High Rate of Response Noted in MCL and CLL With Cirmtuzumab Plus Ibrutinib – Cancer Network

Patients with mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) who were treated with cirmtuzumab and ibrutinib (Imbruvica) in a phase 1/2 trial showed promising responses with and tolerability of therapy, according to data presented at the American Society of Clinical Oncology (ASCO) Annual Meeting.

The majority of the patients demonstrated a significant reduction in tumor sizes, lead study author Hun Ju Lee, MD, assistant professor of medicine in the Department of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center said during the presentation.

ORR for patients with MCL was 83.3% and was 91.1% for patients with CLL. The complete response rates were 38.9% and 14.7% for the MCL and CLL arms, respectively. Ultimately, 94.4% of patients with MCL and 100% of patients with CLL elicited a clinical benefit from the cirtuzumab/ibrutinib regimen.

The median progression-free survival in both cancers was not reached.

Because MCL and CLL are considered incurable, the study aimed to test the efficacy and safety profile of cirmtuzumab, which inhibits tumor promoting activity of onco-embryonic tyrosine kinase receptor ROR1 found in many solid and hematologic cancers, plus ibrutinib in patients with relapsed/refractory MCL or treatment nave or relapsed/refractory CLL.

The study was performed in 3 parts with separate arms. Part 1, for dose escalation; part 2, for dose expansion; and part 3, comparing cirmtuzumab plus ibrutinib with ibrutinib alone in CLL.

Overall, 26 patients with refractory MCL (median age 66.5, 15.4% women) and 34 patients with treatment nave or RR CLL (median age 68, 23.5% women) were enrolled in the study.

For part 1, 12 patients with MCL were enrolled, and 5 into part 2. The median number of prior regimens was 2, including patients relapsing after ibrutinib (n=4), autologous stem-cell transplantation (n=3), autologous stem cell transplantation/allogenic stem cell transplantation (1) and autologous stem cell transplantation /CAR-T (1). For patients with CLL, at least 74% were high risk, as determined by unmutated IGHV, del17p and/or del11q, in parts 1 and 2.

In part 1, cirmtuzumab was given intravenously 5 times every 2 weeks, and then every 4 weeks, at 2 to 16 mg. Three-hundred or 600 mg doses were also examined. Researchers assessed the safety profile of cirmtuzumab during the first 28 days, which was then followed by ibrutinib at approved doses for each indication. A treatment regimen of cirmtuzumab (600 mg) given intravenously 3 times every 2 weeks, and then every 4 weeks, in combination with ibrutinib starting day 0, was chosen as the recommended dosing for parts 2 and 3.

In summary, cirmtuzumab plus ibrutinib is a very well tolerated regimen, Lee noted.

Adverse events with 20% or greater incidence were recorded, including fatigue (n=11), diarrhea (n = 9), contusion (n = 7), dizziness (n = 7) and nausea (n = 7). The efficacy is robust in many of these pre-treated patients, [including] high response, rate durable response [and] encouraging PFS, demonstrating clinical benefit, he concluded.

Of note, the phase 2 study for CLL is completed, and is awaiting a long-term follow-up. Phase 2 for MCL is currently enrolling.

Reference

Lee HJ, Choi M, Siddiqi T, et al. Phase 1/2 study of cirmtuzumab and ibrutinib in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL).J Clin Oncol. 2021;39(suppl 15; abstr 7556).

See the original post:
High Rate of Response Noted in MCL and CLL With Cirmtuzumab Plus Ibrutinib - Cancer Network

Triplet Combo of Polatuzumab Vedotin, Rituximab and Lenalidomide Safe, Effective to Treat Relapsed/Refractory DLBCL – Cancer Network

The novel triplet combination with polatuzumab vedotin (Polivy), rituximab, and lenalidomide was safe while improving overall and complete responses for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to data presented at the 2021 ASCO Annual Meeting.

In this first report of a triplet combination of polatuzumab, rituximab and lenalidomide, the triplet combination showed notable efficacy in a challenging-to-treat relapsed and refractory diffuse large B-cell lymphoma population, said Catherine S.M. Diefenbach, MD, associate professor of medicine, translational director of hematology and director of clinical lymphoma at Perlmutter Cancer Center at NYU Langone Health, during the virtual presentation.

In this phase 1b/2 trial, researchers analyzed the safety of this combination in 57 patients (median age, 71 years; 67% men) with relapsed/refractory diffuse large B-cell lymphoma, were ineligible for or failed prior autologous stem cell transplantation and were treated with at least one prior anti-CD20-containing chemo-immunotherapy regimen. Efficacy of the treatment was assessed in 49 patients (median age, 72 years; 63% men).

The median age was 71, as is typical for this lymphoma, but the age range was from between 28 and 92 years, Diefenbach said.

Most patients in the safety and efficacy groups (86% and 84%, respectively) had stage 3 to 4 disease, nearly a quarter had two lines of therapy (28% and 27%) and nearly a third had three or more lines of therapy (33% and 31%). In addition, some patients underwent previous CAR T-cell therapy (5% and 6%, respectively) or prior bone marrow transplant (11% and 12%).

At induction, all patients received induction during 6 28-day cycles with 1.8 mg/kg of intravenous polatuzumab vedotin, 375 mg/m2 of intravenous rituximab and either a dose escalation of oral lenalidomide (between 10 mg and 20 mg) or the recommended daily dose of the drug on days 1 through 21. Patients who responded to the treatment at the end of induction received 6 months consolidation of 10 mg of lenalidomide (days 1 through 21, monthly) and 375 mg/m2 of rituximab (day 1 every 2 months).

Primary endpoints for this trial included the safety and tolerability of this triplet combination, in addition to complete response rates at the end of induction as assessed by positron emission tomography (PET) scans. Follow-up was conducted for a median of 9.7 months in the safety population and for 9.5 months in the efficacy population.

In the safety population, 75% of patients experienced grade 3 to 4 adverse events, with the most common including neutropenia (58%), thrombocytopenia (14%) and infections (14%). Adverse events led to 26% of patients undergoing a lenalidomide dose reduction and 67% had treatment interruption. One grade 5 adverse event related to the treatment neutropenic sepsis was reported.

The additional (adverse events) were not considered related to study drug, Diefenbach said. For example, a patient who had a fatal gastric hemorrhage who had been enrolled but not yet treated, and a patient with COVID-19 who contracted this disease 167 days after his last dose of the study therapy.

In the efficacy population, the overall response rate was 39% with a complete response rate of 29%. Ten percent of patients had a partial response. Median progression-free survival for the entire population was 6.3 months (95% CI, 4.5-9.7) with a median duration of remission of 8.1 months (95% CI, 4.7-not evaluated) and a median overall survival of 10.9 months (95% CI, 10.9-not evaluated).

However, for the patients who obtained a (complete response) this is 13 patients who were evaluable, the median progression-free survival at 9 months had not been reached, nor has the median overall survival, Diefenbach said. Nearly all patients remain in complete remission.

Additional follow-up is needed to assess the impact of consolidation therapy on the duration of long-term response, Diefenbach said. In summary, the triplet combination of polatuzumab, rituximab and lenalidomide represents a potential novel regimen for patients with transplant-ineligible relapsed and refractory diffuse large B-cell lymphoma and is worthy of further study.

Reference

Magid Diefenbach CS, Abrisqueta P, Gonzalez-Barca E, et al. Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial. J Clin Oncol. 2021;39(suppl 15):Abstract 7512.

Go here to read the rest:
Triplet Combo of Polatuzumab Vedotin, Rituximab and Lenalidomide Safe, Effective to Treat Relapsed/Refractory DLBCL - Cancer Network

Dr. Ghosh on the Role of Off-the-Shelf CAR T-Cell Therapy in Myeloma June – OncLive

Monalisa Ghosh, MD, discusses the role of off-the-shelf CAR T-cell therapy in patients with multiple myeloma.

Monalisa Ghosh, MD, a clinical assistant professor at the University of Michigan, discusses the role of off-the-shelf CAR T-cell therapy in patients with multiple myeloma.

These products are promising in many ways and provide several advantages, including a decreased manufacturing time, Ghosh says. Experts in the field can request and receive off-the-shelf CAR T-cell products from a bank, she explains.This eliminates the need to wait for patient cell collection, which puts the patient at some degree of risk, and decreases the manufacturing time that ordinarily takes several weeks. The decreased treatment timeline can also be beneficial to patients with rapidly progressive disease, Ghosh notes.

However, challenges exist with this therapy, as allogenic cells may cause certain adverse effects, such as a graft-versus-host reaction that is similar to reactions observed with stem cell transplantation, Ghosh says. Currently, certain methods of T-cell receptor engineering may be able to mitigate this risk, she adds.Additionally, some hosts may reject the cells, a possibility that has been observed in early studies, wherein cells have not demonstrated long-term persistence.It may be possible to overcome this through multiple cell infusions, Ghosh notes.

Overall, the accessibility of off-the-shelf CAR T-cell products to a large group of patients with multiple myeloma appears promising, Ghosh concludes.

Original post:
Dr. Ghosh on the Role of Off-the-Shelf CAR T-Cell Therapy in Myeloma June - OncLive

Income, Education Affect Treatment and Survival in MDS – DocWire News

There may be a correlation between income and education and treatment and survival among patients with myelodysplastic syndromes (MDS), according to a study. The results were published in the European Journal of Haematology.

Using the Swedish MDS Register, the researchers identified 2,945 patients diagnosed with MDS between 2009 and 2018. They evaluated relative mortality using Cox regression and treatment differences using Poisson regression. Mortality comparisons were made using a matched group from the general population.

Patients in the lowest income category, compared to the highest, had 50% higher mortality; similarly, those with mandatory school education had 40% higher mortality than those with college or university education. There were also correlations observed between treatment with hypomethylating agents and allogeneic stem cell transplantation (SCT), and investigation with cytogenetic diagnostics, and income and education. Differences in risk class or comorbidity at the time of diagnosis did not account for these differences in mortality and treatment.

In this large, population-based study, we demonstrate that Swedish MDS patients with lower income or shorter education have shorter survival. They are further less likely to be investigated with cytogenetic diagnostics, and less likely to receive treatment with hypomethylating agents, or an allogeneic SCTthe only existing curative treatment for MDS today, the researchers wrote in their conclusion.

Read this article:
Income, Education Affect Treatment and Survival in MDS - DocWire News

Mustang Bio to Host Key Opinion Leader Webinar on MB-106 CD20-Targeted CAR T for – GlobeNewswire

Webinar to be held Tuesday, June 15, 2021, at 1:00 p.m. ET

WORCESTER, Mass., June 07, 2021 (GLOBE NEWSWIRE) -- Mustang Bio, Inc. (Mustang) (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, today announced that it will host a key opinion leader (KOL) webinar on MB-106 CD20-targeted CAR T cell therapy, which is being developed for high-risk B-cell non-Hodgkin lymphomas (B-NHL) and chronic lymphocytic leukemia (CLL), on Tuesday, June 15, 2021, at 1:00 p.m. Eastern Time.

The webinar will feature a presentation by Mazyar Shadman, M.D., M.P.H., Associate Professor at the Fred Hutchinson Cancer Research Center (Fred Hutch), who will discuss interim results from the ongoing Phase 1/2 clinical trial investigating the safety and efficacy of MB-106 CD20-targeted CAR T for B-NHL and CLL. These data have been selected for an e-poster presentation at the European Hematology Association 2021 Virtual Congress (EHA2021), which is being held June 9-17. Dr. Shadman, along with colleague Brian Till, M.D., also an Associate Professor at Fred Hutch, will be available to answer questions following the formal presentations.

Mustangs management team will also provide more details on the planned MB-106 Phase 1/2 clinical trial to be conducted under Mustangs Investigational New Drug (IND) application. The Company recently announced that the U.S. Food and Drug Administration (FDA) accepted its IND to initiate a multicenter Phase 1/2 clinical trial investigating the safety, tolerability and efficacy of MB-106 for relapsed or refractory B-NHL and CLL.

To participate in the webinar, please register here.

About Dr. Shadman Mazyar Shadman, M.D., M.P.H., is an Associate Professor at the University of Washington (UW) and Fred Hutch. He is a hematologic malignancies expert who specializes in treating patients with lymphoma and CLL. Dr. Shadman is involved in clinical trials using novel therapeutic agents, immunotherapy (CAR T cells), and stem cell transplant for treatment of lymphoid malignancies with a focus on CLL. He also studies the clinical outcomes of patients using institutional and collaborative retrospective cohort studies.

Dr. Shadman received his M.D. from Tehran University in Iran. He finished an internal medicine internship and residency training at the Cleveland Clinic in Cleveland, Ohio. He completed his fellowship training in hematology and medical oncology at UW and Fred Hutch. Dr. Shadman also earned an M.P.H. degree from UW and was a fellow for the National Cancer Institutes cancer research training program at Fred Hutch, where he studied cancer epidemiology.

About Dr. Till Brian Till, M.D., is an Associate Professor in the Clinical Research Division of Fred Hutch and Department of Medicine at UW. His laboratory focuses on developing chimeric antigen receptor (CAR)-based immunotherapies for non-Hodgkin lymphoma and understanding why CAR T cell therapies work for some patients but not for others. He led the first published clinical trial testing CAR T cells as a treatment for lymphoma patients. Dr. Till also has a clinical practice treating patients with lymphoma and attends on the stem cell transplantation and immunotherapy services at the Seattle Cancer Care Alliance.

About Mustang Bio Mustang Bio, Inc. is a clinical-stage biopharmaceutical company focused on translating todays medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases. Mustang aims to acquire rights to these technologies by licensing or otherwise acquiring an ownership interest, to fund research and development, and to outlicense or bring the technologies to market. Mustang has partnered with top medical institutions to advance the development of CAR T therapies across multiple cancers, as well as a lentiviral gene therapy for X-linked severe combined immunodeficiency. Mustang is registered under the Securities Exchange Act of 1934, as amended, and files periodic reports with the U.S. Securities and Exchange Commission (SEC). Mustang was founded by Fortress Biotech, Inc. (NASDAQ: FBIO). For more information, visit http://www.mustangbio.com.

ForwardLooking Statements This press release may contain forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934, each as amended. Such statements include, but are not limited to, any statements relating to our growth strategy and product development programs and any other statements that are not historical facts. Forward-looking statements are based on managements current expectations and are subject to risks and uncertainties that could negatively affect our business, operating results, financial condition and stock value. Factors that could cause actual results to differ materially from those currently anticipated include: risks relating to our growth strategy; our ability to obtain, perform under, and maintain financing and strategic agreements and relationships; risks relating to the results of research and development activities; risks relating to the timing of starting and completing clinical trials; uncertainties relating to preclinical and clinical testing; our dependence on third-party suppliers; our ability to attract, integrate and retain key personnel; the early stage of products under development; our need for substantial additional funds; government regulation; patent and intellectual property matters; competition; as well as other risks described in our SEC filings. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as required by law, and we claim the protection of the safe harbor for forward-looking statements contained in the Private Securities Litigation Reform Act of 1995.

Company Contacts: Jaclyn Jaffe and Bill Begien Mustang Bio, Inc. (781) 652-4500 ir@mustangbio.com

Investor Relations Contact: Daniel Ferry LifeSci Advisors, LLC (617) 430-7576 daniel@lifesciadvisors.com

Media Relations Contact: Tony Plohoros 6 Degrees (908) 591-2839 tplohoros@6degreespr.com

See original here:
Mustang Bio to Host Key Opinion Leader Webinar on MB-106 CD20-Targeted CAR T for - GlobeNewswire

Early Promise Observed With Lisaftoclax in Relapsed/Refractory CLL and Other Hematologic Malignancies – Targeted Oncology

Lisaftoclax (APG-2575), a novel BCL-2 inhibitor, has demonstrated encouraging responses with acceptable safety in patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), and other hematologic cancers who were treated in first-in-human phase 1 trial (NCT03537482), according to data presented during the 2021 ASCO Annual Meeting.1

Twelve of 15 evaluable patients with relapsed/refractory CLL/SLL experienced a partial response (PR) to treatment with lisaftoclax, which translated to an objective response rate (ORR) of 80%. In this population, the median number of treatment cycles was 9 (range, 5-24) and the median time to response was 2 cycles (range, 2-8).

Moreover, the BCL-2 inhibitor was also administered to 21 patients with nonCLL/SLL malignancies, which included those with non-Hodgkin lymphoma (NHL; n = 12), multiple myeloma (n = 6), myeloid malignancies (n = 2), and hairy cell leukemia (n = 1). The median duration of treatment in these patients was 3 cycles (range, 1-22). None of these patients were found to achieve a PR or better with lisaftoclax, although 1 patient with multiple myeloma and t(11;14) experienced a minor response to treatment.

Importantly, no dose-limiting toxicities (DLTs) were observed with the agent, even when administered at the highest dose of 1200 mg.

[Lisaftoclax] is a very well-tolerated agent, even up to doses of 1200 mg and has infrequent grade 3 or 4 treatment-related adverse effects [TRAEs]. No tumor lysis syndrome [TLS] or DLT was observed and the maximum-tolerated dose [MTD] has not been reached, Sikander Ailawadhi, MD, lead study author, consultant and professor of medicine, Department of Medicine, in the Division of Hematology/Oncology, at Mayo Clinic, said during a presentation on the data. Our preliminary data suggest proof of concept, with an ORR of 80% in patients with relapsed/refractory CLL or SLL.

Lisaftoclax is a novel, potent, orally active, selective BCL-2 inhibitor that is currently under development. By targeting the antiapoptotic BCL-2 family of proteins, the agent serves to prevent cancer cells from circumventing apoptosis, which would allow for extended survival. Notably, many hematologic malignancies are characterized by having high levels of BCL-2.

Although another BCL-2 inhibitor, venetoclax (Venclexta), has been FDA approved in this space, the agent has been linked with TLS; thus, the agent requires a 5-week ramp-up. Moreover, venetoclax has been found to be associated with other AEs, such as thrombocytopenia and severe neutropenia.2

Previously, in preclinical models of B-cell malignancies, lisaftoclax has proven to be able to selectively target BCL-2 and to demonstrate antitumor activity. When the cell-free kinetics of the agent was compared with venetoclax, the agents appeared to showcase a similar profile, according to Ailawadhi. In a cell line of acute lymphoblastic leukemia, which is BCL-2 driven, selectivity for BCL-2 was again demonstrated by lisaftoclax. Other models have demonstrated that the mechanism of action of the agent allows it to disrupt the BCL-2:BIM complex, which mediates the induction of apoptosis.

In the phase 1 study, investigators set out to evaluate oral lisaftoclax at daily doses ranging from 20 mg to 1200 mg in a 28-day treatment cycle. The clinical trial initially included an accelerated dose escalation with 1 or more patients per dose level.

However, once the dose level reached 400 mg, a DLT was observed, any laboratory or clinical TLS was observed, any hypersensitivity reaction was suspected, 2 grade 2 drug-related toxicities, or 1 or more grade 3 drug-related toxicities were reported, the standard 3+3 dose-escalation design would begin.

At that time, patients were then divided into 1 of 2 cohorts. Patients enrolled to cohort A had non-CLL hematologic malignancies and low risk of TLS, while those enrolled to cohort B had CLL or another hematologic malignancy with intermediate/high risk of TLS. Three to 6 patients were treated per dose level.

Once the MTD was reached or the recommended phase 2 dose (RP2D) was determined, then the dose-expansion phase of the study would begin. Patients received treatment until either progressive disease or intolerable toxicity.

The objectives of the early-phase trial are to examine safety in the form of DLTs, MTD, and RP2D, as well as to characterize the pharmacokinetic (PK) profile of the agent and its efficacy. Key efficacy end points include ORR, progression-free survival, duration of response, overall survival, and minimal residual disease status.

To be eligible for enrollment, patients needed to have histologically confirmed relapsed/refractory CLL/SLL, multiple myeloma, Waldenstrm macroglobulinemia, myeloid malignancies, and NHL, which included diffuse large B-cell lymphoma, follicular lymphoma, and mantle cell lymphoma. Patients also needed to have acceptable hematologic and renal function.

If patients had previously received treatment with a BCL-2 inhibitor; had undergone allogeneic hematopoietic stem cell transplant within 1 year; had Burkitt lymphoma, Burkitt-like lymphoma, or lymphoblastic lymphoma/leukemia; or required concurrent central nervous system therapy, they were excluded.

At the time of the April 15, 2021, data cutoff, a total of 36 patients had been enrolled to the trial. The median age of study participants was 70.0 years (range, 39-89), with 52.8% of patients aged 70 years or older. The majority of patients were male (72.2%) and had a median number of 2 prior therapies (range, 1-13).

Moreover, 58.3% (n = 21) of patients have discontinued treatment, and the most frequently cited reason was because of disease progression (61.9%; n = 13). Other reasons for discontinuation included toxicity (9.5%), patient withdrawal (14.3%), or physician decision (14.3%). One patient was switched to a standard-of-care regimen because of symptomatic anemia, 1 was switched to another option because of hepatitis B reactivation, and 1 was switched to another option because of lack of response to treatment.

The swimmer plot also showed a couple of things of prominence. One, there is a significant proportion of patients who are ongoing on treatment, Ailawadhi noted. Also, youll especially notice in [patients with] CLL, early on, the presence of PRs. A significant number of patients at various dose levels achieved a PReven at the 2-cycle mark. This was something quite prominent and [says something] about the efficacy of the drug.

When looking specifically at patients with non-CLL/SLL malignancies, the clinical benefit rate (CBR) achieved with lisaftoclax was 50.0% (n = 10). Specifically, in those with NHL, multiple myeloma, myeloid malignancy, and hairy cell leukemia, these rates were 63.6% (n = 7), 40.0% (n = 2), 0%, and 100% (n = 1), respectively.

Five of these 21 patients were treated at a dose below 600 mg, Ailawadhi said. Even in these patients, with the single-agent treatment, half the patients had stable disease. This is, in fact, encouraging and warrants further focused development within these disease areas.

When looking at the patients in the CLL/SLL group (n = 15), 14 patients had CLL, and 1 patient had SLL. Moreover, within this subset, 53.3% of patients had stage I to II disease, while 46.7% had stage III or IV disease. When looking at the International Prognostic Index for CLL, 20% of patients were low, 33.3% were intermediate, 40% were high, and 6.7% were very high.

Additionally, 2 patients had del(17p)/TP53 mutation, 1 had del(11q), 3 had CD38 positivity, and 9 patients had unmutated IgVH. All patients previously received CD20 antibody-based therapy, 2 received prior fludarabine, and 4 had prior BTK inhibition. Four patients had bulky disease.

Focusing just on the efficacy within the [patients with] CLL/SLL, we can see a bit more clearly that a lot of patients are still continuing therapyespecially on higher doses, Ailawadhi said. Several patients achieved PR, even early on in their treatment.

Overall, the safety profile of lisaftoclax was found to be favorable. Any-grade treatment-related AEs (TRAEs) were reported in 75% of patients, and these included fatigue (27.8%), neutropenia (22.2%), diarrhea (19.4%), anemia (16.7%), constipation (11.1%), and nausea (11.1%). Grade 3 or higher TRAEswhich occurred in 5% or more of patientswere experienced by 25% of patients and included neutropenia (13.9%), nausea (5.6%), and decreased platelet count (5.6%).

Only 1 patient discontinued treatment with lisaftoclax because of a TRAE, which was grade 2 pruritus and skin sensitivity. Notably, no grade 5 TRAEs were observed.

The MTD was not reached, and no laboratory or clinical TLS has been reported. Itis quite a prominent finding that no TLS was noted in any of the patients on any of the cohorts during the study, at any of those dose levels, Ailawadhi said. In cohort B, which is the high-risk TLS group, 600 mg of [lisaftoclax] has been selected as the RP2D based on the clinical results and the PK/pharmacodynamic profile. In cohort A, there is still 1 slot to be enrolled at the 1200-mg dose after which the RP2D will be determined.

The preliminary PK profile of the agent demonstrated that exposures increased with doses from 20 mg to 1200 mg, with an average half-life ranging from 4 to 8 hours. So, there was some activity at lower doses, as well, Ailawadhi noted.

Additionally, on BH3 profiling, the drug was found to rapidly trigger complex changings in BCL-2 proteins among samples collected from patients with CLL/SLL; these changes were consistent with rapid clinical reductions in absolute lymphocyte counts.

[Lisaftoclax, based on all of these data, holds very good promise as a potential treatment alternative for patients with relapsed/refractory CLL, SLL, or other hematologic malignancies where BCL-2 may be a driver with a significantly shorter daily ramp-up schedule, as against weekly, and a very favorable safety profile based on these data, Ailawadhi concluded.

References

1. Ailawadhi S, Chanan-Khan AAA, Chen Z, et al. First-in-human study of lisaftoclax (APG-2575), a novel BCL-2 inhibitor (BCL-2i), in patients (pts) with relapsed/refractory (R/R) CLL and other hematologic malignancies (HMs). J Clin Oncol. 2021;39(suppl 15):7502. doi:10.1200/JCO.2021.39.15_suppl.7502

2. Davids MS, Hallek M, Wierda W, et al. Comprehensive safety analysis of venetoclax monotherapy for patients with relapsed/refractory chronic lymphocytic leukemia. Clin Cancer Res. 2018;24(18):4371-4379. doi:10.1158/1078-0432.CCR-17-3761

Visit link:
Early Promise Observed With Lisaftoclax in Relapsed/Refractory CLL and Other Hematologic Malignancies - Targeted Oncology

Polatuzumab With Rituximab and Lenalidomide Shown Safe and Effective for Relapsed/Refractory DLBCL – Targeted Oncology

In patients with relapsed/refractory diffuse large B-cell lymphoma treated with the triplet combinaton of polatuzumab vedotin (Polivy), rituximab and lenalidomide, therapy was considered to be safe and effective, according to data presented at the 2021 ASCO Annual Meeting.

In this first report of a triplet combination of polatuzumab, rituximab and lenalidomide, the triplet combination showed notable efficacy in a challenging-to-treat relapsed and refractory diffuse large B-cell lymphoma population, said Catherine S.M. Diefenbach, MD, associate professor of medicine, translational director of hematology and director of clinical lymphoma at Perlmutter Cancer Center at NYU Langone Health, during the virtual presentation.

In this phase 1b/2 trial, researchers analyzed the safety of this combination in 57 patients (median age, 71 years; 67% men) with relapsed/refractory diffuse large B-cell lymphoma, were ineligible for or failed prior autologous stem cell transplantation and were treated with at least one prior anti-CD20-containing chemo-immunotherapy regimen. Efficacy of the treatment was assessed in 49 patients (median age, 72 years; 63% men).

The median age was 71, as is typical for this lymphoma, but the age range was from between 28 and 92 years, Diefenbach said.

Most patients in the safety and efficacy groups (86% and 84%, respectively) had stage 3 to 4 disease, nearly a quarter had two lines of therapy (28% and 27%) and nearly a third had three or more lines of therapy (33% and 31%). In addition, some patients underwent previous CAR T-cell therapy (5% and 6%, respectively) or prior bone marrow transplant (11% and 12%).

At induction, all patients received induction during 6 28-day cycles with 1.8 mg/kg of intravenous polatuzumab vedotin, 375 mg/m2 of intravenous rituximab and either a dose escalation of oral lenalidomide (between 10 mg and 20 mg) or the recommended daily dose of the drug on days 1 through 21. Patients who responded to the treatment at the end of induction received 6 months consolidation of 10 mg of lenalidomide (days 1 through 21, monthly) and 375 mg/m2 of rituximab (day 1 every 2 months).

Primary endpoints for this trial included the safety and tolerability of this triplet combination, in addition to complete response rates at the end of induction as assessed by positron emission tomography (PET) scans. Follow-up was conducted for a median of 9.7 months in the safety population and for 9.5 months in the efficacy population.

In the safety population, 75% of patients experienced grade 3 to 4 adverse events, with the most common including neutropenia (58%), thrombocytopenia (14%) and infections (14%). Adverse events led to 26% of patients undergoing a lenalidomide dose reduction and 67% had treatment interruption. One grade 5 adverse event related to the treatment neutropenic sepsis was reported.

The additional (adverse events) were not considered related to study drug, Diefenbach said. For example, a patient who had a fatal gastric hemorrhage who had been enrolled but not yet treated, and a patient with COVID-19 who contracted this disease 167 days after his last dose of the study therapy.

In the efficacy population, the overall response rate was 39% with a complete response rate of 29%. Ten percent of patients had a partial response. Median progression-free survival for the entire population was 6.3 months (95% CI, 4.5-9.7) with a median duration of remission of 8.1 months (95% CI, 4.7-not evaluated) and a median overall survival of 10.9 months (95% CI, 10.9-not evaluated).

However, for the patients who obtained a (complete response) this is 13 patients who were evaluable, the median progression-free survival at 9 months had not been reached, nor has the median overall survival, Diefenbach said. Nearly all patients remain in complete remission.

Additional follow-up is needed to assess the impact of consolidation therapy on the duration of long-term response, Diefenbach said. In summary, the triplet combination of polatuzumab, rituximab and lenalidomide represents a potential novel regimen for patients with transplant-ineligible relapsed and refractory diffuse large B-cell lymphoma and is worthy of further study.

Reference

Magid Diefenbach CS, Abrisqueta P, Gonzalez-Barca E, et al. Polatuzumab vedotin (Pola) + rituximab (R) + lenalidomide (Len) in patients (pts) with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL): Primary analysis of a phase 1b/2 trial. J Clin Oncol. 2021;39(suppl 15):Abstract 7512.

Go here to read the rest:
Polatuzumab With Rituximab and Lenalidomide Shown Safe and Effective for Relapsed/Refractory DLBCL - Targeted Oncology

FDA Lifts Hold on bluebird bio’s Sickle Cell and Beta-Thalassemia Gene Therapies – BioSpace

Sarah Silbiger/Getty Images

The U.S. Food and Drug Administration (FDA)liftedthe clinical holds on bluebird bios Phase I/II HGB-206 and Phase III HGB-210 studies of LentiGlobin for sickle number disease gene therapy for adults and children and the Phase III Northstar-2 and Northstar-3 trials of betibeglogene autotemcel gene therapy (Zynteglo in the EU and UK) for adults, adolescents and children with transfusion-dependent beta-thalassemia (TDT).

On February 16, bluebird bioplacedits Phase I/II and Phase III trial of LentiGlobin for SCD on temporary suspensions because of a case of acute myeloid leukemia (AML). Another patient from Group C of HGB-206 was suspected of myelodysplastic syndrome (MDS).

LentiGlobin is a gene therapy, which has been granted Orphan Drug Designation, Fast Track Designation, Regenerative Medicine Advanced Therapy (RMAT) Designation, and Rare Pediatric Disease Designation. The Suspected Unexpected Serious Adverse Reaction (SUSAR) was assumed to be linked to the viral vector used to deliver their genetic payloads in the gene therapies.

On April 20, theyreviseda previously reported case of myelodysplastic syndrome (MDS) in its Phase I/II trial of LentiGlobin for SCD but have now decided it is not a case of MDS and revised it to transfusion-dependent anemia.

At the time, Philip Gregory, bluebird bios chief scientific officer, stated, In addition to our earlier findings of several well-known genetic mutations and gross chromosomal abnormalities commonly observed in AML in this patient, our latest analyses identified the integration site for the vector within a gene called VAMP4. VAMP4 has no known association with the development of AML nor with processes such as cellular proliferation or genome stability."

"Moreover, we see no significant gene misregulation attributable to the insertion event. In totality, the data from our assessments provide important evidence demonstrating that it is very unlikely our BB305 lentiviral vector played a role in this case, and we have shared with theFDAthat we believe these results support lifting the clinical holds on our beta-thalassemia and sickle cell disease programs, Gregory said.

Betibeglogene autotemcel (beti-cel) is a one-time gene therapy that adds function copies of a modified form of the beta-globin gene to a patients own hematopoietic stem cells. This has been granted conditional marketing authorization (CMA) under the brand name Zynteglo for patients 12 years and older with TDT in Europe and the UK. It is apparently on hold there while the European Medicines Agency (EMA)s Pharmacovigilance Risk Assessment Committee (PRAC) reviews the therapys safety. The CMA remains valid while the renewal application review is ongoing.

Patient safety continues to be our utmost priority, and we are grateful for the close partnership with the FDA, investigators, scientists and most importantly, patients, who all contributed to the assessments of the adverse events in HGB-206 that ultimately led to todays announcement, said Andrew Obenshain, president, severe genetic diseases, bluebird bio.

"As pioneers in gene therapy, we remain committed to advancing the field through our learnings. Over the past four months, we have gained deeper knowledge and understanding of the pathophysiology of sickle cell disease that will allow us to better serve patients and the broader community," Obenshain continued. "We look forward to resuming our clinical programs and continuing to advance toward major regulatory submissions for sickle cell disease and beta-thalassemia.

Bluebird plans to continue its rolling Biologics License Application (BLA) to the FDA for beti-cel in mid-2021 for adults, adolescents, and children with transfusion dependent beta-thalassemia across all genotypes.

Read the rest here:
FDA Lifts Hold on bluebird bio's Sickle Cell and Beta-Thalassemia Gene Therapies - BioSpace

HSCT-Sparing, Chemotherapy-Free Treatment of Ph+ ALL With Ponatinib/Blinatumomab Leads to 100% CR Rate – Cancer Network

Combination therapy with ponatinib (Iclusig) and blinatumomab (Blincyto) induced a complete response in all patients with Philadelphia chromosome (Ph)positive acute lymphocytic leukemia (ALL) who were treated on a phase 2 study (NCT03263572), according to a presentation at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.1

The chemotherapy-free, hematopoietic stem cell transplant (HSCT)sparing regimen for patients receiving systemic therapy in the first-line (n = 20) led to a complete response (CR) rate or pathologic CR rate of 100%, while patients with relapsed/refractory Phpositive ALL had a rate of 89%. Moreover, patients in the frontline Phpositive cohort had a major molecular response (MMR) of 100% and a complete molecular response (CMR) of 85%.

The combination of ponatinib and blinatumomab is safe and effective in Ph-positive ALL, Nicholas James Short, MD, an assistant professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, said during an oral presentation of the data. Overall, the novel chemotherapy-free combination of ponatinib and blinatumomab appears to be a promising regimen in both frontline and relapsed/refractory Ph-ALL, as well as in chronic myeloid leukemia in lymphoid blast phase [CML-LBP]. Given the particularly favorable outcomes of newly diagnosed patients with frontline, Ph-positive ALL who were not transplanted in first remission, these data suggest that this regimen may serve as an effective transplant-sparing regimen in this population.

Chemotherapy plus a TKI has become the standard of care in newly diagnosed Ph-positive ALL, with first- and second-generation TKIs yielding 5-year overall survival (OS) rates of approximately 35% to 50%.2-4 Moreover, while ponatinib has yielded promising activity in patients with T315I mutations, which are present in up to 75% of patients at relapse,5 blinatumomab has demonstrated efficacy as a monotherapy in the relapsed/refractory setting, and in combination with dasatinib in newly diagnosed patients.6,7

The trial enrolled patients with newly diagnosed or relapsed/refractory Ph-positive ALL, as well as lymphoid accelerated or blast phase CML. Patients who had previously received 1 to 2 courses of chemotherapy with or without a TKI were able to enroll in the newly diagnosed cohort. Additionally, patients needed to be over 18 years of age, with a ECOG performance status of 0-1, and adequate hepatic function in order to enroll.

Patients with uncontrolled or active cardiovascular disease, including a history of myocardial infarction, cardiovascular accident, or revascularization within 3 months; congestive heart failure with reduced left ventricular ejection fraction; atrial of ventricular arrhythmia; a history of arterial or venous thromboembolism; or uncontrolled hypertension were not able to enroll on the study. Additional exclusion criteria included significant central nervous system (CNS) pathology with the exception of CNS leukemia.

Patients received a 30 mg induction dose of ponatinib and a standard dose of blinatumomab on a 4 weeks on, 2 weeks off schedule. From there, patients received up to 4 consolidation cycles of the regimen followed by maintenance ponatinib for 5 years, the dose of which decreased to 15 mg daily once patients achieved a CMR. All patients were given 12 doses of intrathecal chemotherapy with an altering administration of cytarabine and methotrexate.

The primary of end point of the trial was CMR rate in the frontline cohort, and CR/pathologic CR rate in the relapsed/refractory setting. Key secondary end points included event-free survival (EFS), OS, and safety.

To date, 20 frontline patients have been treated, 10 with relapsed/refractory disease, and 5 with CML-LBP, Short explained. The median age of the frontline cohort was 62 years [range, 34-83]. Among the 10 patients with relapsed/refractory Ph-positive ALL, 1 was primary refractory to [a] previous regimen, 4 were treated in first salvage, and 5 in second or later salvage. Among the 5 patients with CML-LBP, 3 had not received any prior therapy for blast phase disease, 1 was treated in first salvage, and 1 in second salvage.

Additional data indicated that the cohort of patients with CML-LBP had a CR or pathologic CR rate of 100%, as well as an MMR rate of 60%, and CMR rate of 40%. Moreover, the relapsed/refractory cohort achieved a rate of 88% in both MMR and CMR. In total, the overall patient population had a CR or pathologic CR rate of 96%, an MMR rate of 91%, and a CMR rate of 79%. No patients were reported to have an early death while on the study.

After the first cycle of treatment, the frontline ALL cohort had a CMR rate of 58%, an MMR rate of 26%, and 16% did not experience a response. Moreover, 75% of patients in the relapsed/refractory ALL cohort, and 20% in the CML-LBP cohort had a CMR after the first cycle, while 25% and 80% of patients from both cohorts did not respond, respectively.

Of the patients who experienced a CR or pathologic CR in the frontline ALL arm (n = 20), 1 died following CR due to post-procedural bleeding and hypovolemic shock, while 19 continue to experience ongoing responses without the need for stem cell transplantation. Notably, no patients in this have relapsed within 6 months.

In the relapsed/refractory ALL cohort, of the patients who responded (n = 9), 4 went on to receive HSCT, 1 of whom relapsed and died. Another patient relapsed and developed T315I and E255V mutations at relapse. Overall, 3 patients from this cohort are experiencing an ongoing response without the need for HSCT, while 1 patient died off study due to unknown causes.

In the CML-LBP arm, 2 responders (n = 5) relapsed, one of whom developed myeloid blast phase disease but is currently alive and in remission, while the other developed L248V and Y253H mutations at relapse but is currently alive and in remission following HSCT. Additionally, 3 patients continue to experience an ongoing response without HSCT.

After a median follow up of 12 months, the overall patient population is estimated to have 1- and 2-year EFS of 76% and 70%, respectively. Moreover, the estimated 1-year and 2-year OS were 93% and 80%, respectively. Notably, the relapsed/refractory AML cohort had an estimated 1- and 2-year EFS of 61% and 41%, respectively, as well as an estimated 1- and 2-year OS of 80% and 53%, respectively. Additionally, the CML-LBP arm had 60% estimated EFS rate at 1 and 2 years, respectively, as well as a 100% estimated 1- and 2-year rate.

Notably, there were no grade 4 or higher adverse effects (AEs) reported on the study. Common grade 3 AEs related to ponatinib in patients with ALL included elevated lipase (6%), alanine aminotransferase increase (ALT; 3%), cerebrovascular ischemia (3%), hypertension (3%) pancreatitis (3%), and deep vein thrombosis (3%). Grade 2 AEs included rash (11%), ALT increase (3%), and cerebrovascular ischemia (3%) and grade 1 AEs included rash (11%) and ALT increase (3%).

Although most AEs related to blinatumomab were grade 1 or 2 in patients with ALL, 1 patient developed grade 3 encephalopathy that was resolved by corticosteroids and treatment interruption, according to Short. Common grade 2 AEs included cytokine release syndrome (6%) and tremors (3%), as well as 1 patient who developed grade 1 tremors.

References

1. Short NJ, Kantarjian H, Konopleva MY, et al. Combination of ponatinib and blinatumomab in Philadelphia chromosome-positive acute lymphoblastic leukemia: Early results from a phase II study. Presented at: 2021 ASCO Annual Meeting; June 4-8, 2021; Virtual. Abstract 7001.

2. Daver N, Thomas D, Ravandi F, et al. Final report of a phase II study of imatinib mesylate with hyper-CVAD for the front-line treatment of adult patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Haematologica. 2015;100(5):653-651. doi:10.3324/haematol.2014.118588

3. Ravandi F, OBrien S, Cortes J, et al. Long-term follow-up of phase II study of chemotherapy plus dasatinib for the initial treatment of patients with Philadelphia-chromosome positive acute lymphoblastic leukemia. Cancer. 2015;121(23):4158-4164. doi:10.1002/cncr.29646

4. Rousselot P, Coud MM, Gokbuget N, et al. Dasatinib and low-intensity chemotherapy in elderly patients with Philadelphia chromosomepositive ALL. Blood. 2016;126(6):774-782. doi:10.1182/blood-2016-02-700153

5. Jabbour E, Short NJ, Ravandi F, et al. Combination of hyper-CVAD with ponatinib as first-line therapy for patients with Philadelphia chromosome-positive acute lymphoblastic leukaemia: long-term follow-up of a single-centre, phase 2 study. Lancet Haematol. 2018;5(12):e618-e627. doi:10.1016/S2352-3026(18)30176-5

6. Martinelli G, Boissel N, Chevallier P, et al. Complete hematologic and molecular response in adult patients with relapsed/refractory Philadelphia chromosome-positive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase II, single-arm, multicenter study. J Clin Oncol. 2017;35(16):1795-1802. doi:10.1200/JCO.2016.69.3531

7. Fo R, Bassan R, Vitale A, et al. Dasatinibblinatumomab for Ph-positive acute lymphoblastic leukemia in adults. N Engl J Med. 2020;383:1613-1623. doi:10.1056/NEJMoa2016272

See the original post here:
HSCT-Sparing, Chemotherapy-Free Treatment of Ph+ ALL With Ponatinib/Blinatumomab Leads to 100% CR Rate - Cancer Network

Abecma Continues to Improve Survival in Heavily Pretreated Patients With Multiple Myeloma – Curetoday.com

Abecma (idecabtagene vicleucel ; ide-cel; formerly bb2121), a chimeric antigen receptor (CAR)-T cell therapy, led to improved survival in patients with multiple myeloma who have been treated with many other lines of therapy, according to updated results from the KarMMa trial presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.1

The favorable benefit risk profile of ide-cel, regardless of the number of prior lines of therapy, supports its role as a treatment option for heavily pretreated relapse refractory multiple myeloma, Dr. Larry D. Anderson, associate professor, UT Southwestern Medical Center, said during a presentation of the poster.

At the December 21, 2020, data cutoff, the average follow-up was 24.8 months (range, 1.7-33.6).

Overall response rate (ORR) the percentage of patients who responded to the treatment was 73% in the overall population, including a 33% complete response rate, where disease could not be detected (CRR; complete response [CR] or stringent complete response [sCR]), 20% with a very good partial response (VGPR), and 20% who had a partial response (PR). ORR rates were 50%, 69%, and 81%, respectively, across the 150, 300, and 450 million CAR T cell-dose arms, including CR/sCR rates of 25%, 29%, and 39%.

Of note, ORR did not vary by the number of prior lines of therapy received. For those who received three prior lines of therapy (a total of 15 patients), the ORR was 73%, including a CRR of 53% and VGPR of 20%, compared with an ORR of 73% in those who received four or more (112 patients) lines of therapy, including a CRR of 30%, VGPR of 23%, and PR of 20%.

Average duration of response (DOR; the time patients disease was stable or in remission after being treated) was 10.9 months, including 9.9 months for the 300 million CAR T cells-dose arm and 11.3 months for the 450 million CAR T cells-dose arm -dose arm. Median DOR was 21.5 months in patients who experienced a CR or sCR. Median DOR by response were 21.5 months among those who experienced a CR; 10.4 months for those with VGPR; and 4.5 months in those with PRs.

Moreover, the rate of event-free 24-month DOR appeared to be similar in patients who received three or four or more lines of therapy. For those who received three lines of prior therapy, median DOR was eight months, compared with 10.9 months in those who received four or more lines of therapy.

Average progression-free survival (PFS) meaning the length of time after treatment when the disease does not get worse was 8.6 months across all target doses, including 5.8 months for the 300 million CAR T cells-dose arm and 12.2 months for the 450 million CAR T cells-dose arm -dose arm. Similarly, average PFS was similar among those who previously received three lines of therapy, compared with four or more prior lines of therapy (8.6 months vs 8.9 months, respectively).

On average, it took patients about one month to respond to therapy and about 2.8 months to experience a CR.

Median overall survival (OS) was 24.8 months, including a median OS of 22.0 months in those who received three lines of prior therapy and 25.2 months in those who received four or more lines of prior therapy. Moreover, OS was 20 months or longer across several key high-risk subgroups, including those aged 65 or older (21.7 months), those with extramedullary disease (20.2 months), and those with triple refractory disease (21.7 months).

Regarding side effects, cytokine release syndrome (CRS; the effect of many inflammatory cytokine immune cells being release into the blood stream) and neurotoxicity (brain and/or nervous system damage) rates were similar, regardless of prior lines of therapy received, and were mostly low grade. In total, 85% and 18% of the overall population experienced at least 1 CRS or neurotoxicity event, respectively.

The safety profile of Abecma was consistent with long-term follow-up, with similar rates of infections and secondary primary malignancies, and no unexpected gene therapy related toxicities were observed. The most common grade 3 to 4 side effects in the overall population were neutropenia (89%), anemia (61%), thrombocytopenia (52%), leukopenia (39%), lymphopenia (27%) and infections (27%).

Long-term results from the KarMMA trial continue to demonstrate frequent, deep, and durable responses in heavily pretreated patients with [relapsed/refractory multiple myeloma], the study authors write in the poster. ORR, CRR, DOR and PFS were consistent with previous reports and patients received similar benefit regardless of the number of prior lines of therapy.

In his presentation, Anderson presented data on long-term efficacy and safety following treatment with Abecma in the pivotal phase 2 KarMMa trial (NCT03361748)-including overall data and by prior line of therapy that patients had received (three compared to four or more), since the FDA label is requiring at least four prior lines, and this study only required three, he added.

In total, 140 patients who had received at least three prior lines of therapy for multiple myeloma including an IMiD, a PI, and an anti-CD38 antibody and were refractory to their last treatment regimen, were enrolled in the study. However, only 128 patients received infusion with Abecma.

Patients were treated with Abecma across the target dose range of 150 (four patients), 300 (70 patients), and 450 (54 patients) million CAR T cells.

ORR served as the primary end point of the study. Secondary end points included CRR, safety, DOR, PFS, OS, pharmacokinetics, minimal residual disease, quality of life and health economics and outcomes research.

At the start of the trial, the average patient age was 61 years (range, 33-78) and patients had a median of six years (range, 1-18) since their diagnosis. A majority of the patients were male (59%), had high tumor burden (51%), B-cell maturation antigen (BCMA) expression 50% or more at screening (85%), ECOG performance status which measures how functional a patient is on a range of 1 (fully functioning) to 5 (dead) of 1 (53%), and Revised International Staging System disease stage of II (70%). Thirty-five percent of patients had high-risk features.2

The median number of prior therapies was six (range, 3-16) and 94% had previously undergone at least one autologous hematopoietic stem cell transplant (94%). Eighty-eight percent of patients required bridging therapy, a kind of pre-treatment before CAR-T cell thearpy. Eighty-nine percent of patients had double-refractory disease, 84% were triple-refractory and 26% were penta-refractory.

Patients who had received three prior lines of therapy had similar baseline characteristics, compared with those who received four or more prior lines, including differences in extramedullary disease, high-risk cytogenetics, prior refractoriness and time since the initial diagnosis to screening.

Patients with relapsed/refractory multiple myeloma previously exposed to immunomodulatory agents, protease inhibitors, and anti-CD38 antibodies have poor outcomes with subsequent therapy using previously approved regimens, with expected response rates in the 26% to 31% range, PFS in the two- to four-month range, and overall survival less than nine months, Anderson explained.

However, the BCMA-directed CAR-T cell therapy previously demonstrated favorable tolerability with deep, durable responses in patients who were heavily pretreated with relapsed/refractory multiple myeloma.As a result, the FDA approved the agent for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior therapies, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody, representing the first BCMAdirected CAR T-cell therapy approved.

The study authors noted that is being explored in ongoing clinical trials, including the following:

Go here to read the rest:
Abecma Continues to Improve Survival in Heavily Pretreated Patients With Multiple Myeloma - Curetoday.com