Efficacy and follow‐up of humanized anti‐BCMA CAR‐T cell therapy in relapsed/refractory multiple myeloma patients with extramedullary‐extraosseous, extramedullary‐bone related, and without extramedullary disease

Idecabtagene vicleucel (ide-cel), a novel chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA), has recently gained approval by the US FDA for relapsed and refractory multiple myeloma (RRMM) after multicenter trials have demonstrated unprecedented results in this difficult-to-treat subgroup of patients. As the first CAR T-cell product approved for myeloma, ide-cel is poised to become a practice-changing treatment option. This first-in-class therapeutic offers hope for more durable remissions, as well as better quality of life, following a single infusion in a group of patients that previously had little hope. This paper reviews the ide-cel product in terms of design, pharmacology, efficacy and toxicity as described in studies reported to date.

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BCMA-Targeted CAR-T Cell Therapy for Relapsed/Refractory Multiple Myeloma

Case Medical Research ◽

10.31525/ct1-nct04271644 ◽

2020 ◽

Author(s):

Keyword(s):

Multiple Myeloma ◽

T Cell ◽

Cell Therapy ◽

T Cell Therapy ◽

Refractory Multiple Myeloma ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T

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Anti-BCMA CAR T administration in a relapsed and refractory multiple myeloma patient after COVID-19 infection: a case report

Journal of Medical Case Reports ◽

10.1186/s13256-020-02598-0 ◽

2021 ◽

Vol 15 (1) ◽

Author(s):

D. Madduri ◽

S. Parekh ◽

T. B. Campbell ◽

F. Neumann ◽

F. Petrocca ◽

...

Keyword(s):

Multiple Myeloma ◽

Case Report ◽

T Cell ◽

Cell Therapy ◽

T Cell Therapy ◽

Refractory Multiple Myeloma ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T ◽

History Of

Abstract Background Very little is known about the risk that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral infection poses to cancer patients, many of whom are immune compromised causing them to be more susceptible to a host of infections. As a precautionary measure, many clinical studies halted enrollment during the initial surge of the global Novel Coronavirus Disease (COVID-19) pandemic. In this case report, we detail the successful treatment of a relapsed and refractory multiple myeloma (MM) patient treated with an anti-B cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T cell therapy immediately following clinical recovery from COVID-19. Case presentation The 57 year old Caucasian male patient had a 4-year history of MM and was considered penta-refractory upon presentation for CAR T cell therapy. He had a history of immunosuppression and received one dose of lymphodepleting chemotherapy (LDC) the day prior to COVID-19 diagnosis; this patient was able to mount a substantial immune response against the SARS-CoV-2 virus, and antiviral antibodies remain detectable 2 months after receiving anti-BCMA CAR T cell therapy. The recent SARS-CoV-2 infection in this patient did not exacerbate CAR T-associated cytokine release syndrome (CRS) and conversely the CAR T cell therapy did not result in COVID-19-related complications. One month after CAR T cell infusion, the patient was assessed to have an unconfirmed partial response per International Myeloma Working Group (IMWG) criteria. Conclusion Our case adds important context around treatment choice for MM patients in the era of COVID-19 and whether CAR T therapy can be administered to patients who have recovered from COVID-19. As the COVID-19 global pandemic continues, the decision of whether to proceed with CAR T cell therapy will require extensive discussion weighing the potential risks and benefits of therapy. This case suggests that it is possible to successfully complete anti-BCMA CAR T cell therapy after recovery from COVID-19. CRB-402 study registered 6 September 2017 at clinicaltrials.gov (NCT03274219).

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Efficacy of Humanized Anti-BCMA CAR T Cell Therapy in Relapsed/Refractory Multiple Myeloma Patients With and Without Extramedullary Disease

Frontiers in Immunology ◽

10.3389/fimmu.2021.720571 ◽

2021 ◽

Vol 12 ◽

Author(s):

Haobin Deng ◽

Meijing Liu ◽

Ting Yuan ◽

Huan Zhang ◽

Rui Cui ◽

...

Keyword(s):

Multiple Myeloma ◽

T Cell ◽

Cell Therapy ◽

M Protein ◽

T Cell Therapy ◽

Hematopoietic Stem ◽

Extramedullary Disease ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T

In recent years, many new treatments for relapsed/refractory (R/R) multiple myeloma (MM) have improved patient prognosis, but the prognosis of patients with extramedullary MM is still particularly poor. Therefore, more efficacious therapies and novel strategies are urgently needed for these patients. The aim of this study was to observe and compare the efficacy and safety of humanized anti-B cell maturation antigen (anti-BCMA) chimeric antigen receptor (CAR) T cell therapy in R/R MM patients with and without extramedullary disease. Seven R/R MM patients with extramedullary disease and 13 without extramedullary disease received humanized anti-BCMA CAR T cell therapy. The overall response rate was not different between patients with and without extramedullary disease. There was no difference in the progression-free survival (PFS) or overall survival (OS) rates between the two groups at 180 days, but the PFS and OS rates in patients with extramedullary disease were lower at 360 days than those in patients without extramedullary disease. Although some patients with extramedullary disease experienced further disease progression, their M protein level did not increase. We did not see this change trend of M protein in patients without extramedullary disease. However, this was not observed in patients without extramedullary disease. Among patients who responded to CAR T cell therapy, the grades of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxic syndrome (ICANS) were much higher among patients with extramedullary disease. In summary, R/R MM patients with extramedullary disease could benefit from humanized anti-BCMA CAR T cell therapy in the short term, although the CRS and ICANS grades were much higher in patients with extramedullary disease. Therefore, anti-BCMA CAR T cell therapy allows for a remission time for R/R MM patients with extramedullary disease, which could be maintained by bridging hematopoietic stem cell transplantation, radiotherapy, and other therapies.Clinical Trial Registrationhttp://www.chictr.org.cn/index.aspx, identifiers ChiCTR1800017051 and ChiCTR2000033925.

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