Multiple Myeloma Draft Evidence Report

March 11, 2021 

Steven D. Pearson, MD
President 
Institute for Clinical and Economic Review
Two Liberty Square, Ninth Floor 
Boston, MA 02109 

RE: Institute for Clinical and Economic Review — Multiple Myeloma Review Draft Evidence Report 

Dear Dr. Pearson: 

The undersigned organizations, who participate in a CAR T-cell therapy working group, appreciate the opportunity to respond to the draft evidence report on Anti B-Cell Maturation Antigen CAR T-cell and Antibody Drug Conjugate Therapy for Heavily Pre-Treated Relapsed and Refractory Multiple Myeloma. 

CAR T-cell therapy (CAR T) is a transformative therapy that can substantially improve outcomes for patients with specific types of cancer. ¹ Jung IY, Lee J. Unleashing the Therapeutic Potential of CAR-T Cell Therapy Using Gene-Editing Technologies. Mol Cells. 2018;41(8):717-723. doi:10.14348/molcells.2018.0242  While there are currently four approved CAR T therapies, there are over 630 active clinical trials, including those for Multiple Myeloma, two of which are being reviewed in this report. ² Approved Cellular and Gene Therapy Products. U.S. Food and Drug Administration website. Accessed February 17, 2021. https://www.fda.gov/vaccines-blood-biologics/cellular-gene-therapy-products/approved-cellular-and- gene-therapy-products , ³ Clinical Trials Finder. American Society of Gene and Cell Therapy website. Accessed February 17, 2021. Asgct.careboxhealth.com

Both idecabtagene vicleucel and ciltacabtagene autoleucel have yet to be approved and studied in real world settings. We remain concerned that the clinical and financial data utilized are premature for the evaluation of CAR-T for Multiple Myeloma. The clinical benefits to patients receiving CAR T for Multiple Myeloma are still evolving, and new studies testing these treatments in earlier lines of care explore the possibility that they may be more effective. ⁴ García-Guerrero E, Sierro-Martínez B, Pérez-Simón JA. Overcoming Chimeric Antigen Receptor (CAR) Modified T-Cell Therapy Limitations in Multiple Myeloma. Front Immunol. 2020;11:1128. Published 2020 Jun 5. doi:10.3389/fimmu.2020.01128 , ⁵ Garfall AL, Dancy EK, Cohen AD, et al. T-cell phenotypes associated with effective CAR T-cell therapy in postinduction vs relapsed multiple myeloma. Blood Adv. 2019;3(19):2812-2815. doi:10.1182/bloodadvances.2019000600  

Below, we highlight several areas that we recommend ICER further consider. 

CAR T Challenges & Patient Population 

With the potential approval of CAR T for Multiple Myeloma approaching, there is significant excitement about the possibility to improve the lives of many patients impacted by the disease. 

Multiple Myeloma patients eligible for CAR T are usually at the point where they have limited alternate treatment options and a very poor chance of survival, with data showing median overall survival without CAR T at 3.4 to 9.3 months. ⁶ Gandhi UH, Cornell RF, Lakshman A, et al. Outcomes of patients with multiple myeloma refractory to CD38- targeted monoclonal antibody therapy. Leukemia. 2019;33(9):2266-2275. doi:10.1038/s41375-019-0435-7  CAR T for Multiple Myeloma have demonstrated an overall survival of over 19 months. ⁷ Munshi NC, et al. Idecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): initial KarMMa results. ASCO 2020 Virtual Scientific Program. Abstract #39T850339T.  Research has also shown that the “cyclical nature” of Multiple Myeloma can result in higher levels of anxiety, depression and fatigue. ⁸ 2020 Cancer Experience Registry Report. Cancer Support Community. https://www.cancersupportcommunity.org/2020CancerExperienceRegistryReport. Accessed March 5, 2021. We have heard first-hand from patients about the value of hope, and that having another option can provide a mindset shift to those facing these circumstances. 

Studies show that many Multiple Myeloma patients experience significant quality of life impacts, including physical symptoms of the disease and side effects of treatment. ⁹ Stewart AK, Dimopoulos MA, Masszi T, et al. Health-Related Quality-of-Life Results From the Open-Label, Randomized, Phase III ASPIRE Trial Evaluating Carfilzomib, Lenalidomide, and Dexamethasone Versus Lenalidomide and Dexamethasone in Patients With Relapsed Multiple Myeloma. Journal of Clinical Oncology. 2016;34(32):3921-3930. doi:10.1200/jco.2016.66.9648  The ongoing psychosocial impacts on patients, caregivers, and family members are also great. ¹⁰ Sherman AC, Simonton S, Latif U, Plante TG, Anaissie EJ. Changes in Quality-of-Life and Psychosocial Adjustment among Multiple Myeloma Patients Treated with High-Dose Melphalan and Autologous Stem Cell Transplantation. Biology of Blood and Marrow Transplantation. 2009;15(1):12-20. doi:10.1016/j.bbmt.2008.09.023 , ¹¹ Molassiotis A, Wilson B, Blair S, Howe T, Cavet J. Living with multiple myeloma: experiences of patients and their informal caregivers. Support Care Cancer. 2011;19(1):101-111. doi:10.1007/s00520-009-0793-1  Physical ailments can include neurological damage such as peripheral neuropathy; pain management issues; kidney failure caused by Multiple Myeloma; and more, having a substantial impact on quality of life. Specifically, in a survey of approximately 200 multiple myeloma patients, 65% said that fatigue interferes with their daily life, 38% were at risk for clinically significant levels of anxiety, and 33% were at risk for clinically significant levels of depression. ¹² 2020 Cancer Experience Registry Report. Cancer Support Community. https://www.cancersupportcommunity.org/2020CancerExperienceRegistryReport. Accessed March 5, 2021.

Health Disparities 

Multiple Myeloma is twice as common in Black people. ¹³ Cancer Facts & Figures for African Americans. American Cancer Society. https://www.cancer.org/research/cancer-facts-statistics/cancer-facts-figures-for-african-americans.html. Accessed March 5, 2021.  ICER addresses concerns about health disparities in the draft evidence report. Specifically, ICER suggests that complex and higher-cost therapies have been underutilized by historically disadvantaged populations, suggesting that breakthrough treatments like CAR T may worsen health disparities. 

We recognize the critical need to ensure that all therapies – including the most innovative – are available to all people living with multiple myeloma, particularly those from historically disadvantaged populations. We look forward to working with ICER and all relevant stakeholders to ensure equitable access. 

Additional Patient Perspectives are Needed 

We recognize and appreciate ICER’s inclusion of patient and caregiver perspectives in the report. The significant physical, emotional, and financial burden on patients being treated for Multiple Myeloma should continue to be a focal point of these analyses. 

ICER takes into account the impact that side effects have on patients, however it is critical that ICER understand the value of a “one and done” therapy. Numerous treatments and regular physician and hospital visits impose a financial burden on both patients and caregivers, including loss of work and/or societal contributions, in addition to direct costs of assuming the role of family caregiver. ¹⁴ Goodwin JA, Coleman EA, Sullivan E, et al. Personal financial effects of multiple myeloma and its treatment. Cancer Nurs. 2013;36(4):301-308. doi:10.1097/NCC.0b013e3182693522  These challenges can be significantly disruptive to the daily life of patients and caregivers. ¹⁵ 2020 Cancer Experience Registry Report. Cancer Support Community. https://www.cancersupportcommunity.org/2020CancerExperienceRegistryReport. Accessed March 5, 2021.

In conclusion, thank you for the opportunity to provide comments on this draft evidence report document. We believe that innovative treatments like CAR T represent hope for patients and caregivers. If you have any questions regarding our comments, please do not hesitate to reach out to our organizations. 

Sincerely, 

American Society for Gene and Cell Therapy
BMT InfoNet 
Cancer Support Community
CLL Society 
Myeloma Crowd