Maximilian Merz, Associate Professor at Joan and Sanford I. Weill Medical College of Cornell University, shared on LinkedIn:
“Please check out our new article in Journal of Hematology and Oncology
CAR T cells vs. bispecific antibodies in early relapsed myeloma
One of the most debated questions in myeloma right now is whether CAR T cells or bispecific antibodies should be used at early relapse.
With CAR T – cells and bispecifics now being tested in newly diagnosed and high – risk smoldering disease, this question will soon move into the frontline.
Placing hazard ratios, response rates and adverse – event frequencies side by side across trials does not give the full picture. Each trial enrolled a different population, and the shared control arm shows this clearly.
Median PFS with a DPd – type control was:
- Apollo (lenalidomide – refractory subgroup): 9.9 mo
- Cartitude: – 4: 11.8 mo
- MajesTEC-3: 18.1 mo
- MonumenTAL – 3: 24.4 mo
That is a 2.5 – fold range for essentially the same regimen.
We performed a systematic review and anchored Bayesian network meta – analysis of 4 randomized phase 3 trials (n = 2,174), covering cilta – cel, Tec – Dara and Tal – Dara Pom. We reconstructed pseudo – individual patient data and reported fixed – and random – effects models side by side. We re – estimated the network in a frequentist framework and analyzed OS as restricted mean survival time (RMST).
Key findings:
PFS point estimates favored Tec – Dara under fixed effects. Once between – trial heterogeneity was accounted for, every contrast crossed unity.
OS was concordant across regimens.
Toxicity profiles differ by modality (CAR T – specific delayed neurotoxicity vs. infections with continuous BCMA engagement vs. GPRC5D on – target effects). However, their overall burden cannot be reliably compared across trials.
Financial toxicity matters too. Using US list prices, cilta – cel is a one – time cost. The continuously dosed regimens exceed it within the first year. Cost per progression – free month was $18,300 for cilta-cel vs. $43,452 for Tec-Dara, $34,976 for Tal-Dara and $58,629 for Tal-Dara-Pom. Fixed-duration bispecific strategies could close this gap.
Bottom line: Randomized evidence shows no significant efficacy differences between these regimens in early relapse. It also does not demonstrate equivalence. Until head – to – head data exist, treatment selection should integrate patient – and disease – related factors, toxicity, sequencing, access and cost.
Huge thanks to this outstanding international team: João Tadeu Souto Filho, Peter Voorhees, Hermann Einsele, Fredrik Schjesvold, Edward Cliff, maria victoria mateos manteca, Vania Hungria, Yael C. Cohen, Carlos Fernandez de Larrea, Meral Beksac, C. Ola Landgren, M.D., Ph.D., Saad Z. Usmani, Luciano J Costa, Nico Gagelmann
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