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Patients With Penta-Refractory Myeloma May Benefit From BCMA-Directed Therapy


Researchers noted that despite the promising findings, more novel treatments are needed to overcome the disease’s resistance.

Patients with penta-relapsed refractory multiple myeloma (RRMM) exhibited a significant survival benefit after receiving B-cell maturation antigen (BCMA)-directed therapy (BDT), compared with those who used non-BDT, according to results of a new retrospective analysis. The findings were published in the journal Cancers.

Penta-refractory myeloma is defined as refractoriness to the 5 main myeloma treatments, including lenalidomide, pomalidomide, bortezomib, carfilzomib, and either daratumumab or isatuximab, researchers explained. Because it does not respond adequately to standard treatment approaches, the disease poses a challenge to providers.

However, initial clinical trials have indicated that BCMA, a novel target for plasma cells, shows promising results in patients with refractory myeloma.

“BCMA therapy comes in 3 main forms: antibody drug conjugates (ADC), chimeric antigen receptor T (CAR T)-cell therapy, and bispecific T-cell engagers (BiTEs),” authors explained.

In an effort to evaluate survival outcomes of patients with penta-RRMM treated with BDT, researchers assessed 78 patients with data collected from the University of Kansas Medical Center between January 2015 and July 2022.

Researchers defined myeloma refractoriness as “a progression within 60 days of a drug-containing regimen or a response less than the partial response (PR).”

Median patient age was 65 years, and 29 patients had Revised International Staging System (R-ISS) stage III disease. The majority of patients had high-risk cytogenetics, and 45 had extramedullary disease. Patients also had a median of 5 (range, 3-12) lines of therapy prior to their penta-refractory state.

Of the individuals included in the study, 43 were treated with BDT and 35 were not treated with BDT.

Analyses revealed:

  • Type of BDT received included belantamab mafodotin (55%), CAR T-cell therapy (40%), BCMA monoclonal antibody (28%), and BiTEs (5%)
  • Eleven (25%) patients received more than one BDT
  • No significant differences were identified between baseline characteristics for the 2 groups
  • Patients treated with a BDT had better median overall survival at 17 vs 6 months, (HR, 0.3; P < .001.)
  • Poor performance status, White race, and high-risk cytogenetics were associated with worse outcomes, whereas using a BDT was associated with better outcomes

Worse outcomes in White patients could be due to a small sample size included in the current study, though more investigation is needed.

“Our study defines a new benchmark for contemporary expectations for survival,” the authors wrote, also noting that the findings “underscored a sizable proportion of patients with high-risk cytogenetics and extramedullary disease, reflecting the current expectations of an increased percentage of high-risk disease features with each relapse.”

“We believe that the refractory status of myeloma is more prognostic than the number of prior lines of therapy,” they added.

As resistance to specific drug classes can play a crucial role in determining treatment response, going forward, trials ought to focus on drug class refractoriness. This way, therapies can be better tailored to patients and researchers can develop more effective treatments for individuals with RRMM, the authors said.

The single-center and retrospective nature of the study are limitations, but the researchers note the data reflect the largest “real-life” cohort of penta-RRMM patients to their knowledge.

Findings also highlight the need for treatment guidelines for penta-refractory disease.

“This study underscores the importance of reporting the refractory disease status in clinical trials in addition to/instead of the numbers of prior lines of therapy,” authors concluded. “BCMA-targeting drugs with novel mechanisms of action are needed and can improve the outcomes of patients with penta-RRMM."


Atrash S, Mammadzadeh A, Peng F, et al. Outcomes of penta-refractory multiple myeloma patients treated with or without BCMA-directed therapy. Cancers. Published online May 24, 2023. doi:10.3390/cancers15112891

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