Details

Autor(en) / Beteiligte

• Frerichs, Kristine A.
• Minnema, Monique C.
• Levin, Mark-David
• Broijl, Annemiek
• Bos, Gerard M.J.
• Kersten, Marie José
• Mutis, Tuna
• Verkleij, Christie P.M.
• Nijhof, Inger S.
• Maas-Bosman, Patricia W.C.
• Klein, Saskia K.
• Zweegman, Sonja
• Sonneveld, Pieter
• van de Donk, Niels W.C.J.

Titel

Efficacy and safety of daratumumab combined with all-trans retinoic acid in relapsed/refractory multiple myeloma

Ist Teil von

• Blood advances, 2021-12, Vol.5 (23), p.5128-5139

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The efficacy of daratumumab depends partially on CD38 expression on multiple myeloma (MM) cells. We have previously shown that all-trans retinoic acid (ATRA) upregulates CD38 expression and reverts daratumumab-resistance ex vivo. We therefore evaluated the optimal dose, efficacy, and safety of daratumumab combined with ATRA in patients with daratumumab-refractory MM in a phase 1/2 study (NCT02751255). In part A of the study, 63 patients were treated with daratumumab monotherapy. Fifty patients with daratumumab-refractory MM were subsequently enrolled in part B and treated with daratumumab (reintensified schedule) combined with ATRA until disease progression. The recommended phase 2 dose of ATRA in combination with daratumumab was defined as 45 mg/m2. At this dose, the overall response rate (ORR) was 5%, indicating that the primary endpoint (ORR ≥15%) was not met. However, most patients (66%) achieved at least stable disease. After a median follow-up of 43 months, the median progression-free survival (PFS) for all patients was 2.8 months. Patients who previously achieved at least a partial response or minimal response/stable disease with prior daratumumab monotherapy had a significantly longer PFS compared with patients who immediately progressed during daratumumab as single agent (median PFS 3.4 and 2.8 vs 1.3 months). The median overall survival was 19.1 months. The addition of ATRA did not increase the incidence of adverse events. Flow cytometric analysis revealed that ATRA temporarily increased CD38 expression on immune cell subsets. In conclusion, the addition of ATRA and reintensification of daratumumab had limited activity in patients with daratumumab-refractory MM, which may be explained by the transient upregulation of CD38 expression. This trial was registered at www.clinicaltrials.gov as #NCT02751255. •The combination of daratumumab with ATRA is safe but has limited activity in patients with daratumumab-refractory MM.•The limited efficacy may be partially explained by the transient increase in CD38 expression upon ATRA treatment. [Display omitted]