Results of comparison of the efficacy and safety of monotherapy with monoclonal anti-CD38 antibodies in patients with relapsed/refractory multiple myeloma in real practice and clinical trials.

Abstract

Relevance. Over the past decades, there has been significant progress in increasing the overall survival (OS) of patients with relapsed/refractory multiple myeloma (RRMM) [1, 2]. Despite this, the search for new therapeutic options to improve the effectiveness of RRMM therapy continues [3]. The recent inclusion of anti-CD38 monoclonal antibodies (mAbs) in clinical practice has provided significant progress in the therapy of patients with RRMM [3, 4]. Purpose of the study. To conduct a retrospective comparative analysis of our own experience with the use of anti-CD38 mAbs (daratumumab, isatuximab) as monotherapy for RRMM in the population of patients participating in clinical trials (CTs) and from real-world clinical practice (RCP). Materials and methods. The present analysis includes data from 63 patients with RRMM who were treated from 06.2016 to 06.2020 at the MMNC named after S. P. Botkina was administered monotherapy with daratumumab (n=58) or isatuximab (n=5). The key inclusion criterion in the discussed CTs was a history of ≥3 lines of previous treatment, including a proteasome inhibitor and an immunomodulator, or refractoriness to both drugs. Patients had not previously received anti-CD38 therapy. In the RCP group, there were 6 patients with ECOG ≥3, which was not allowed in the CTs. Daratumumab and isatuximab were administered in standard doses, the cycle duration was 28 days. Therapy was administered until progression, death, or unacceptable toxicity. Result. With a median follow-up of 20 months. (1-62 months) the overall response rate of patients in CT was higher than in RCTs (50% vs. 29.3%, respectively), as was OS - median 26.5 vs. 17.0 months, respectively. No differences were found between the groups in terms of progression-free survival (median 5 and 6 months, respectively). Infusion reactions (IR) associated with the use of anti-CD38 mAbs occurred mainly at the first administration (>90% of cases) and did not exceed grade 1-2. Conclusion. The results of anti-CD38 mAb monotherapy in RCTs are inferior to those in patients included in international CTs. Based on experience/results, the primary use of anti-CD38 mAb in monotherapy is indicated in heavily pretreated patients with depleted bone marrow hematopoiesis reserves and accumulated organ toxicity, when the administration of intensive triplets may be accompanied by excessive adverse events. Switching from the intravenous form of daratumumab to the subcutaneous form allows to reduce the administration time of the drug from several hours to 3-5 minutes and thereby reduce the incidence of IR.

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