Updated Results from the Phase I CRB-402 Study of Anti-Bcma CAR-T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma: Correlation of Expansion and Duration of Response with T Cell Phenotypes

Alsina, Melissa; Shah, Nina; Raje, Noopur; Jagannath, Sundar; Madduri, Deepu; Kaufman, Jonathan L.; Siegel, David S.; Munshi, Nikhil C.; Rosenblatt, Jacalyn; Lin, Yi; Jakubowiak, Andrzej; Jasielec, Jagoda; Timm, Alison; Turka, Ashley; Mao, Pingping; Martin, Nathan; Campbell, Timothy B.; Hege, Kristen; Bitter, Hans; Petrocca, Fabio; Berdeja, Jesús G.

doi:10.1182/blood-2020-140410

Cited by 75 publications

(58 citation statements)

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“…Several other BCMA-targeted CAR-T cell products are under investigation in phase I/II studies, starting from bb21217, constructed on the basis of bb2121 CAR structure with an extra domain of bb007 to enrich for T cells displaying a memory-like phenotype to allow a longer persistence. A phase I CRB-402 study 85 evaluated bb21217 in 62 patients with a median of six prior lines of therapy (range: 3–17; 64% triple-refractory) who received CAR-T cells dose ranging from 150 to 450⨰10 6 . Overall, ORR was 68% with 54% achieving at least VGPR and 29% CR/sCR.…”

Section: “Old” Generation Immunotherapiesmentioning

confidence: 99%

Novel Experimental Drugs for Treatment of Multiple Myeloma

Offidani

Corvatta²,

Morè

et al. 2021

JEP

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Multiple myeloma (MM) is the second most frequent hematological malignancy characterized by bone marrow aberrant plasma cells proliferation leading to a genetic complex and heterogeneous disease, with a median survival ranging from two to more than 10 years. By using new drugs such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs) in different combinations and high-dose therapy followed by auto-transplantation, there has been an amazing improvement in the outcome of this disease in recent years. Despite this, MM is still considered an incurable disease, characterized by remission periods alternated with relapse/progression episodes finally leading to resistant disease. In particular, patients who become refractory to PIs, IMiDs and mAbs have a very poor outcome. Moreover, to overcome resistant residual disease, a large combination of drugs will be increasingly used in early lines of therapy; this further reduces the therapeutic options at each relapse. This natural history means that MM always needs new drugs/strategies to overcome the incoming resistance. New combinations of naked mAbs are becoming the therapy of choice for patients refractory to lenalidomide and/or PI; conjugated mAbs will be useful in triple- and more-refractory patients; CAR-T cells and bispecific mAbs have shown relevant results in very advanced stages of disease. In this review, we reported the results of these new therapies and explored their potential applications. Personalized and precision medicine seem to be the new frontier of cancer treatment. Although no single or few factors have been identified as disease drivers in MM, recurrent gene mutations were recognized and specific compounds targeting these alterations were developed and studied. Therefore, we reviewed these targeted drugs to try to understand what the best therapeutic strategy in MM is.

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Section: “Old” Generation Immunotherapiesmentioning

confidence: 99%

Novel Experimental Drugs for Treatment of Multiple Myeloma

Offidani

Corvatta²,

Morè

et al. 2021

JEP

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“…In the phase I CRB-402 study, patients with heavily pretreated relapsed/refractory MM had high rates of very good partial responses (VGPRs) or better to the anti-BCMA CAR T cell therapy bb21217, according to updated results presented at the 2019 American Society of Hematology (ASH) Annual Meeting [ 25 ]. At a follow-up ranging from 1 to 35 months, the tumor response was 68%, ranging from 43% to 83%, depending on the dose [ 26 ]. Higher doses appear to be associated with better responses.…”

Section: Anti-bcmacar T-cell Studiesmentioning

confidence: 99%

CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma

Martino

Canale

Alati

et al. 2021

Cancers

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Despite the improvement in survival outcomes, multiple myeloma (MM) remains an incurable disease. Chimeric antigen receptor (CAR) T-cell therapy targeting B-cell maturation antigen (BCMA) represents a new strategy for the treatment of relapsed/refractory MM (R/R). In this paper, we describe several recent advances in the field of anti-BCMA CAR T-cell therapy and MM. Currently, available data on anti-BCMA CART-cell therapy has demonstrated efficacy and manageable toxicity in heavily pretreated R/R MM patients. Despite this, the main issues remain to be addressed. First of all, a significant proportion of patients eventually relapse. The potential strategy to prevent relapse includes sequential or combined infusion with CAR T-cells against targets other than BCMA, CAR T-cells with novel dual-targeting vector design, and BCMA expression upregulation. Another dark side of CART therapy is safety. Cytokine release syndrome (CRS) andneurologic toxicity are well-described adverse effects. In the MM trials, most CRS events tended to be grade 1 or 2, with fewer patients experiencing grade 3 or higher. Another critical point is the extended timeline of the manufacturing process. Allo-CARs offers the potential for scalable manufacturing for on-demand treatment with shorter waiting days. Another issue is undoubtedly going to be access to this therapy. Currently, only a few academic centers can perform these procedures. Recognizing these issues, the excellent response with BCMA-targeted CAR T-cell therapy makes it a treatment strategy of great promise.

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“…The bb21217 CAR-T cells are produced by culturing Ide-cel with a PI3K inhibitor. 44 Clinically, bb21217 is undergoing a Phase 1 multicenter study for MM patients who received ≥3 prior regimens, including PI and IMiD agents. Investigators published initial results on 44 patients.…”

Section: Multiple Myeloma Car-t Cells In Clinical Trialsmentioning

confidence: 99%

A Review of Chimeric Antigen Receptor T-Cell Therapy for Myeloma and Lymphoma

Atrash¹,

Moyo²

2021

OTT

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Collectively, hematological malignancies account for the fourth most common malignancy. Myeloma and lymphoma are the most common types of hematological malignancies. Unfortunately, the management of refractory myeloma and lymphoma remains challenging. The discovery of new immunological therapies, namely chimeric antigen receptors T cells (CAR-T), outlined unprecedented B cell malignancies results. In this context, the CAR-T-based approach has led to the proliferation of many clinical studies. In this review, we will deal with the CAR-T structure, and we will summarize the primary clinical studies assessing the risks and benefits of CAR-T cell therapy. We will also deal with the adverse events and management of cytokine release syndromes/immune effector cell-associated neurotoxicity syndrome (ICANS). Subsequently, we will review potential future improvements to overcome refractoriness and improve expansion while decreasing CAR-T’s off-target effects. The advances in the CAR-T platform represent a step forward with promising unlimited future possibilities that made it a paradigm-shifting for the management of B cell malignancies.

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Updated Results from the Phase I CRB-402 Study of Anti-Bcma CAR-T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma: Correlation of Expansion and Duration of Response with T Cell Phenotypes

Cited by 75 publications

References 0 publications

Novel Experimental Drugs for Treatment of Multiple Myeloma

Novel Experimental Drugs for Treatment of Multiple Myeloma

CART-Cell Therapy: Recent Advances and New Evidence in Multiple Myeloma

A Review of Chimeric Antigen Receptor T-Cell Therapy for Myeloma and Lymphoma

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