Daratumumab May Attenuate Cardiac Dysfunction Related to Carfilzomib in Patients with Relapsed/Refractory Multiple Myeloma: A Prospective Study

Abstract

Carfilzomib has improved survival in patients with relapsed/refractory multiple myeloma (RRMM), but it may exert cardiovascular adverse events (CVAEs). The aim of this study was to assess whether treatment with daratumumab may ameliorate carfilzomib-related toxicity. We prospectively evaluated 25 patients with RRMM who received either daratumumab in combination with carfilzomib and dexamethasone (DaraKd) (n = 14) or Kd (n = 11). Cardiac ultrasound was performed before treatment initiation and C6D16 or at the time of treatment interruption. Patients were followed for a median of 10 months for CVAEs. The mean (± SD) age was 67.8 ± 7.6 years and 60% were men. The two treatment groups did not significantly differ in baseline demographic characteristics (p > 0.1 for all). In the DaraKd group, we did not observe any significant change in markers of ventricular systolic function. However, these markers deteriorated in the Kd group; left ventricular (LV) ejection fraction, LV global longitudinal strain, tricuspid annular plane systolic excursion and RV free wall longitudinal strain significantly decreased from baseline to second visit (p < 0.05). A significant group interaction (p < 0.05) was observed for the abovementioned changes. CVAEs occurred more frequently in the Kd than the DaraKd group (45% vs. 28.6%). DaraKd was associated with preserved post-treatment cardiac systolic function and lower CVAE rate compared with Kd. The clinical significance and the underlying mechanisms merit further investigation.

Daratumumab Treatment for “Truly Frail” Elderly Myeloma Patients

“…Among the treatment options for MM, CFZ in particular is expected to have a high efficacy, but concerns about cardiotoxicity arise in routine clinical practice. However, there have been several reports suggesting that the combination of CFZ with DARA may attenuate these concerns [ 68 , 125 ]. This is welcome news for elderly MM patients who often have multiple comorbidities.…”

Cardiac toxicities in multiple myeloma: an updated and a deeper look into the effect of different medications and novel therapies

“…Cardiovascular adverse events occurred more frequently in the Kd than the KdD group (45% vs. 28.6%). KdD was associated with preserved post-treatment cardiac systolic function and lower CVAE rate compared with Kd [ 39 ]. The mechanism behind this speculated cardioprotective effect, although not fully understood, could be related to inhibition (by daratumumab) of ectoenzymatic activity on the coenzyme NADP+, however this still needs additional exploration and evaluation for confirmation.…”

IMiD-Free Interval and IMiDs Sequence: Which Strategy Is Better Suited for Lenalidomide-Refractory Myeloma?

“…Regarding exposure and safety, PI might be a more suitable option than POM in combination with the anti-CD38 MoAb because the incidence of dose reduction due to hematological toxicity is more frequent with anti-CD38 MoAb plus POM than that with PI [12,52]. In addition, CD38 downregulation may induce increased coronary flow and prevent cardiac toxicity caused by PI [92,93]. In terms of therapeutic activity, the PI and anti-CD38 MoAb combination can enhance ADCC by downregulating HLA class A [94,95] and complement-dependent cytotoxicity (CDC) by downregulating CD55 and CD59 [96].…”