The Power of the Immune System: New Treatment for Painful Blood Cancer Side Effect – Curetoday.com

Using BK virus (BKV)-specific T cells from healthy donors to treat BKV-associated hemorrhagic cystitis, a painful side effect associated with immunosuppression from stem cell transplants, may relieve the complication faster in patients with lymphoma or leukemia, according to trial results.

What was very important was that within a week of giving the cells, the majority of patients symptoms improved, Dr. Katy Rezvani, professor of stem cell transplantation and cellular therapy at The University of Texas MD Anderson Cancer Center in Houston and lead study author, said in an interview with CURE. The effect of the cells is relatively rapid.

BKV-associated hemorrhagic cystitis occurs more frequently in patients with leukemia or lymphoma who received a treatment of allogeneic stem cell transplantation. As a result, it can lead to patients having blood in their urine and passing clots, which can cause urinary retention (difficulty urinating or completely emptying the bladder) and, in more severe cases, kidney disease.

In patients who receive stem cell transplants, those who have a half match (when patients only have some genetic similarities with the donors immune system) are at an increased risk for BKV-associated hemorrhagic cystitis because they are more immunosuppressed. Approximately 40% of patients who have a half match develop this complication.

In the phase 2 trial, BKV-specific T cells, which recognize and attack BKV, from healthy donors were given once intravenously, with the option to receive additional doses every two weeks if needed. Of the 59 patients enrolled in the trial, 67.7% had complete (all symptoms resolved) or partial (almost all symptoms resolved) responses within 14 days. This increased to 81.6% after 28 days.

Some intolerance was observed in patients who were previously treated with steroids, which can kill T cells. There were no side effects, and there were no reports of new liver or gastrointestinal graft-versus-host disease (GVHD, occurs when the donor's cells attack the patient's cells) associated with the antiviral T cells, aside from a few cases of skin GVHD that quickly resolved with corticosteroids.

This treatment has the potential to stop the vicious cycle that comes with the current standard of care, which consists of hospitalization with continuous bladder irrigation (using a catheter to wash out the bladder) and morphine infusion to help patients tolerate the pain, according to Rezvani.

This outpatient treatment is preventing patients from having to be admitted (to the hospital), which is wonderful because patients come into hospital with one thing, they stay in the hospital for a few weeks, then they develop other complications, Rezvani explained. They start getting other infections, they get pneumonia, they become malnourished, etc.

According to Rezvani, one donor can produce up to 50 doses of T cells, which are frozen until needed. Every time the patient comes (into the hospital), within 24 hours we can treat them, she said.

Of note, the therapy is only available at MD Anderson, so patients with the complication would need to travel to the health center to receive it an option that may not be possible because of physical condition or finances. Im hoping that we will get to a situation where well be able to start a multicenter study at some point, Rezvani said, which would make the care more accessible to patients. In the meantime, I think the greatest limitation really is that patients will have to come to MD Anderson to receive the treatment, and for many patients with the terrible BKV hemorrhagic cystitis, this is not obviously possible.

Until then, Rezvani is focusing on the next generation of the treatment: genetically modifying BKV-specific T cells that are more resistant to steroids, thus broadening the patient spectrum that the treatment could help.

Its important to realize that the use of immunotherapy against viruses and cancers (has) opened up a very exciting new era of treatment for our patients, she concluded. We are learning a lot more from the immune system (and are harnessing) the power of the immune system to fight infections and cancers. ... I think the field is going to continue to grow, and many more such treatments to target both viruses and cancers (are) going to become available.

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The Power of the Immune System: New Treatment for Painful Blood Cancer Side Effect - Curetoday.com

Global Cell Therapy Market Research Report 2021: Opportunities with the Approval of Kymriah and Yescarta Across Various Countries -…

DUBLIN--(BUSINESS WIRE)--The "Global Cell Therapy Market Size, Share & Trends Analysis Report by Use-type, by Therapy Type (Autologous, Allogenic), by Region (North America, Europe, Asia Pacific, Latin America, MEA), and Segment Forecasts, 2021-2028" report has been added to ResearchAndMarkets.com's offering.

The global cell therapy market size is expected to reach USD 23.0 billion by 2028 and is expected to expand at a CAGR of 14.5% from 2021 to 2028.

The emergence of new technologies to support the development of advanced cellular therapies has aided in market growth. Companies are leveraging new technologies not only for the expansion of their product portfolio but also for establishing out-licensing or co-development agreements with other entities to support their product development programs.

Cell-based therapies hold great potential for replacing, repairing, restoring, or regenerating damaged tissues, and organs. Researchers are making huge investments in the development of such effective and safe treatments as an alternative to conventional treatment strategies which can be further attributed to the market growth.

Out of all therapeutic areas, oncology has the highest number of ongoing clinical trials. T cells, CD34+ and/or CD133+ stem cells, mesenchymal stem/stromal cells are predominantly employed for clinical investigation.

The majority of biopharmaceutical entities have been affected by the COVID-19 pandemic, while several cellular therapy development companies have witnessed a strongly negative impact, which can be attributed to complications in logistics as well as the manufacturing models employed in this industry. In addition, substantial and stable funding is imperative to ensure successful commercial translation of cell-based therapeutics, a factor that was negatively affected in 2020, further affecting the market growth.

A survey conducted recently among executives of more than 15 European and U.S. cellular therapy companies indicated that disruption caused by the pandemic was significant, which demanded market entities to create strategies to sustain themselves and plan the next wave of innovative therapies.

Key issues faced by companies operating in the market include on-time delivery of therapies to patients at required clinical sites. In addition, the administration of these therapeutics poses several post-pandemic challenges. Hospitals are hesitant in offering services, owing to concerns over transmission of SARS-CoV-2, particularly to vulnerable individuals. Moreover, patients have not been able to visit cellular therapy centers either, owing to the lockdowns and travel bans.

Cell Therapy Market Report Highlights

Market Dynamics

Market driver analysis

Market restraint analysis

Market opportunity analysis

COVID-19 Impact Analysis

Challenges analysis

Opportunities analysis

Challenges in manufacturing cell therapies against COVID-19

Companies Mentioned

For more information about this report visit https://www.researchandmarkets.com/r/n1u89x

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Global Cell Therapy Market Research Report 2021: Opportunities with the Approval of Kymriah and Yescarta Across Various Countries -...

Pursuing Optimal Therapy Remains a Challenge in Indolent B-Cell Lymphoma – Targeted Oncology

A significant proportion of patients worldwide live disease-free for a decade or longer following first-line therapy, with various approaches suggesting that there may be pathways to develop approaches for a cure for at least a subset of patients

Follicular lymphoma (FL) and other forms of indolent non-Hodgkin lymphoma (iNHL) are commonly considered incurable diseases with continual risk of relapse over time, shorter durations of response with each subsequent line of therapy, and a risk of transformation to a more aggressive B-cell lymphoma. Although these lymphomas are characterized as indolent, one of the most common causes of death for these patients is lymphoma.1 On the other hand, a significant proportion of patients worldwide live disease-free for a decade or longer following first-line therapy, with various approaches suggesting that there may be pathways to develop approaches for a cure for at least a subset of patients.1-5 In the Indolent B-Cell Lymphoma session during the Society of Hematologic Oncology 2021 Annual Meeting, 4 presentations were explored: Molecular Pathogenesis of Follicular Lymphoma and Its Relevance to Clinical Practice, Sequencing Therapy in Follicular Lymphoma, Novel Therapies in Indolent Lymphoma, and CAR T-Cell Therapy in Indolent Lymphoma in lectures by world-class experts Jessica Okosun, MA, MB BChir, MRCP, FRCPath, PhD, Peter Martin, MD, Loretta Nastoupil, MD, and Caron Jacobson, MD, MMSc.

Next-generation sequencing studies, led by Michael R. Green, PhD, Dr Okosun, and others, have described the panoply of genomic events involved in FL and have aided in identifying candidate genetic drivers.6-9 This work clarified the diverse genomic landscape and the temporal clonal dynamics of FL. Common genomic events that occur with t(14;18) include high frequencies of mutations affecting epigenetic regulation, disruptions in pathways such as those involved in immune recognition (eg, TNFRSF14), NF-KB (eg, CARD11), and JAK/STAT signaling (eg, STAT6).9,10 Next-generation sequencing also has been used to examine factors associated with progression of FL, transformation of iNHL to more aggressive lymphomas, and spatial heterogeneity in FL. Recent studies have explored the subclonal diversity and spatial heterogeneity observed among patients with FL that have potential clinical implications for the development of prognostic and predictive biomarkers and targeted treatment strategies. For instance, exome sequencing of FL tumors and paired germline have identified nonsynonymous somatic variants corresponding to missense (81%), indels (10%), nonsense (7%), and splice site (2%) changes.6 This work revealed spatially discordant mutations in genes such as EZH2 and EP300. One attractive treatment paradigm emerging from this work involves specifically targeting highly recurrent and truncal gene mutations that have roles in FL pathogenesis. Other studies did not identify a single compelling genetic event responsible for transformation, but instead suggest that the acquisition of certain genetic alterations may result in aggressive transformation.7,9,11 Exploration of the FL genomics in this session can clarify stratified treatment approaches targeting specific early genetic lesions identified in FL and may eventually provide strategies to eradicate these cell populations and provide pathways to cure FL.

In the past decade, many new agents have been introduced for the management of FL, and therapeutic strategies have evolved over time. Recently, my co-chair in this session, Nathan Fowler, MD, and I reviewed data from trials addressing the safety and efficacy of lenalidomide alone and in combination with rituximab as a first-line therapy and as a treatment of patients with relapsed/refractory FL.12 However, since that review other agents have received FDA approval for patients with relapsed FL. There is considerable variation in response rates for recently approved therapies ranging from objective response rates of 40% to 60% for PI3K inhibitors, 35% to 65% for EZH2 inhibitors, and greater than 70% for autologous stem cell transplantation, and CD19-directed chimeric antigen receptor (CAR) T-cell therapy.13-18 Recently approved therapies in relapsed FL have commonly been based on response rate and duration of response (DOR) demonstrated in phase 2 studies. However, despite numerous trials performed in the field, there is no single standard of care for patients with iNHL who are undergoing second-line treatment or beyond.

As a result of the patterns of relapse and transformation associated with iNHL, the clinical treatment of patients with FL and other iNHLs often requires multiple lines of therapy using various regimens with different mechanisms of action.19-22 The clinical benefits and adverse effects associated with the treatments available at relapse vary and are influenced by patient and disease characteristics at the time of progression, the duration of the interval from last treatment, and the toxicity and responses associated with the treatments previously administered. This results in a marked heterogeneity of clinical situations encountered during the treatment of these patients. Some patients with iNHL will remain well treated using available treatments, whereas others will develop disease refractory to conventional approaches and become candidates for novel treatments and clinical trials. Additional real-world data regarding patient characteristics at relapse, patterns of care, expectations of response rates and duration, and survival outcomes are lacking in the setting of relapsed and refractory iNHL. To help inform treatment decisions by health care providers treating patients with iNHL in this complex and evolving treatment landscape, Dr Martin will describe approaches for sequencing therapies. To optimally individualize treatment strategies for patients with previously untreated and relapsed iNHL, the risks and benefits of the available options should be well known. This lecture will enable providers to effectively discuss the goals of therapy with the patient at each intervention, which is also critical in providing an optimal sequence of therapy.

Although many patients with FL experience long or possibly near-normal life expectancies, there remains persistent variability in patient outcomes.19-22 Patients who relapse within 2 years of first-line chemoimmunotherapy or with histologic transformation are at risk for early mortality and are high-priority candidates for novel treatment strategies evaluated in clinical trials.23-25 Prior studies have demonstrated diminishing DOR by line of therapy.26,27

However, variability of iNHL disease biology, treatment options, and treatment patterns complicate outcome assessments based on line of therapy alone. Several novel and targeted therapies are being developed and evaluated in patients with relapsed iNHL, including cereblon inhibitors, antiCD20-CD3 bispecific antibodies, and additional anti-CD19 CAR T-cell therapies. Dr Nastoupil will provide key insights on the novel therapies available for patients in clinical trials and those that are establishing pathways toward applications in clinical settings.

CAR therapy targeting CD19 is one promising treatment for patients with relapsed or refractory FL and CD19+ iNHLs. Patients who are candidates for CAR T-cell therapy often have symptomatic disease that could be fatal if left untreated. Dr Jacobson will discuss strategies for bridging therapy, which may include chemotherapy, targeted therapy, or radiation therapy; approved and experimental CAR T-cell approaches for FL and iNHLs; and describe traditional and novel adverse events and outcomes from clinical trials involving CAR T-cell therapy.

REFERENCES:

1. Sarkozy C, Maurer MJ, Link BK, et al. Cause of death in follicular lymphoma in the first decade of the rituximab era: a pooled analysis of French and US cohorts. J Clin Oncol. 2019;37(2):144-152. doi:10.1200/JCO.18.00400

2. Bachy E, Seymour JF, Feugier P, et al. Sustained progression-free survival benefit of rituximab maintenance in patients with follicular lymphoma: long-term results of the PRIMA study. J Clin Oncol. 2019;37(31):2815-2824. doi:10.1200/JCO.19.01073.

3. Becnel MR, Nastoupil LJ, Samaniego F, et al. Lenalidomide plus rituximab (R 2 ) in previously untreated marginal zone lymphoma: subgroup analysis and long-term follow-up of an open-label phase 2 trial. Br J Haematol. 2019;185(5):874-882. doi:10.1111/bjh.15843

4. Strati P, Jain P, Johnson RJ, et al. Long-term follow-up of lenalidomide and rituximab as initial treatment of follicular lymphoma. Blood. 2021;137(8):1124-1129. doi:10.1182/blood.2020007994

5. Watanabe T, Tobinai K, Wakabayashi M, et al; JCOG0203 Collaborators. Outcomes after R-CHOP in patients with newly diagnosed advanced follicular lymphoma: a 10-year follow-up analysis of the JCOG0203 trial. Lancet Haematol. 2018;5(11):e520-e531. doi:10.1016/S2352-3026(18)30155-8

6. Araf S, Wang J, Korfi K, et al. Genomic profiling reveals spatial intra-tumor heterogeneity in follicular lymphoma [published correction appears in Leukemia. 2019;33(6):1540]. Leukemia. 2018;32(5):1261-1265. doi:10.1038/s41375-018-0043-y

7. Green MR, Gentles AJ, Nair RV, et al. Hierarchy in somatic mutations arising during genomic evolution and progression of follicular lymphoma. Blood. 2013;121(9):1604-1611. doi:10.1182/blood-2012-09-457283

8. Green MR, Kihira S, Liu CL, et al. Mutations in early follicular lymphoma progenitors are associated with suppressed antigen presentation. Proc Natl Acad Sci U S A. 2015;112(10):E1116-E1125. doi:10.1073/pnas.1501199112

9. Okosun J, Bdr C, Wang J, et al. Integrated genomic analysis identifies recurrent mutations and evolution patterns driving the initiation and progression of follicular lymphoma. Nat Genet. 2014;46(2):176-181. doi:10.1038/ng.2856

10. Kumar E, Pickard L, Okosun J. Pathogenesis of follicular lymphoma: genetics to the microenvironment to clinical translation. Br J Haematol. Published online March 10, 2021. doi:10.1111/bjh.17383

11. Okosun J, Montoto S, Fitzgibbon J. The routes for transformation of follicular lymphoma. Curr Opin Hematol. 2016;23(4):385-391. doi:10.1097/MOH.0000000000000255

12. Flowers CR, Leonard JP, Fowler NH. Lenalidomide in follicular lymphoma. Blood. 2020;135(24):2133-2136. doi:10.1182/blood.2019001751

13. Dreyling M, Santoro A, Mollica L, et al. Phosphatidylinositol 3-kinase inhibition by copanlisib in relapsed or refractory indolent lymphoma. J Clin Oncol. 2017;35(35):3898-3905. doi:10.1200/JCO.2017.75.4648

14. Flinn IW, Miller CB, Ardeshna KM, et al. DYNAMO: a phase II study of duvelisib (IPI-145) in patients with refractory indolent non-Hodgkin lymphoma. J Clin Oncol. 2019;37(11):912-922. doi:10.1200/JCO.18.00915

15. Gopal AK, Kahl BS, de Vos S, et al. PI3K inhibition by idelalisib in patients with relapsed indolent lymphoma. N Engl J Med. 2014;370(11):1008-1018. doi:10.1056/NEJMoa1314583

16. Jacobson C, Chavez JC, Sehgal AR, et al. Primary analysis of zuma-5: a phase 2 study of axicabtagene ciloleucel (axi-cel) in patients with relapsed/refractory (r/r) indolent non-Hodgkin lymphoma (iNHL). Blood. 2020;136(suppl 1):40-41. doi:10.1182/blood-2020-136834

17. Metzner B, Pott C, Mller TH, et al. Long-term clinical and molecular remissions in patients with follicular lymphoma following high-dose therapy and autologous stem cell transplantation. Ann Oncol. 2013;24(6):1609-1615. doi:10.1093/annonc/mds657

18. Morschhauser F, Tilly H, Chaidos A, et al. Tazemetostat for patients with relapsed or refractory follicular lymphoma: an open-label, single-arm, multicentre, phase 2 trial. Lancet Oncol. 2020;21(11):1433-1442. doi:10.1016/S1470-2045(20)30441-1

19. Flowers CR, Leonard JP, Nastoupil LJ. Novel immunotherapy approaches to follicular lymphoma. Hematology Am Soc Hematol Educ Program. 2018;2018(1):194-199. doi:10.1182/asheducation-2018.1.194

20. Leonard JP, Nastoupil LJ, Flowers CR. Where to start? Upfront therapy for follicular lymphoma in 2018. Hematology Am Soc Hematol Educ Program. 2018;2018(1):185-188. doi:10.1182/asheducation-2018.1.185

21. Nastoupil LJ, Flowers CR, Leonard JP. Sequencing of therapies in relapsed follicular lymphoma. Hematology Am Soc Hematol Educ Program. 2018;2018(1):189-193. doi:10.1182/asheducation-2018.1.189

22. Salles G. How do I sequence therapy for follicular lymphoma? Hematology Am Soc Hematol Educ Program. 2020;2020(1):287-294. doi:10.1182/hematology.2020000156

23. Casulo C, Byrtek M, Dawson KL, et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare Study. J Clin Oncol. 2015;33(23):2516-2522. doi:10.1200/JCO.2014.59.7534

24. Casulo C, Friedberg JW, Ahn KW, et al. Autologous transplantation in follicular lymphoma with early therapy failure: a National LymphoCare Study and Center for International Blood and Marrow Transplant Research analysis. Biol Blood Marrow Transplant. 2018;24(6):1163-1171. doi:10.1016/j.bbmt.2017.12.771

25. Casulo C, Nastoupil L, Fowler NH, Friedberg JW, Flowers CR. Unmet needs in the first-line treatment of follicular lymphoma. Ann Oncol. 2017;28(9):2094-2106. doi:10.1093/annonc/mdx189

26. Batlevi CL, Sha F, Alperovich A, et al. Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups. Blood Cancer J. 2020;10(7):74. doi:10.1038/s41408-020-00340-z

27. Link BK, Day BM, Zhou X, et al. Second-line and subsequent therapy and outcomes for follicular lymphoma in the United States: data from the observational National LymphoCare Study. Br J Haematol. 2019;184(4):660-663. doi:10.1111/bjh.15149

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Pursuing Optimal Therapy Remains a Challenge in Indolent B-Cell Lymphoma - Targeted Oncology