Abstract
Background: Although with the introduction of novel agents, clinical outcomes have significantly
improved in patients of multiple myeloma (MM); however, nearly all relapse, requiring
subsequent treatment. Patients who have been heavily treated for relapsed/refractory
MM (RRMM) have limited options and poor survival outcomes. Carfilzomib plus daratumumab
combination have been evaluated in a phase 1b study in patients of RRMM progressing
after 1–3 lines of therapies including bortezomib and an immune-modulatory drug. However,
data are lacking evaluating the efficacy of this combination in RRMM patients who
have progressed or have suboptimal response on either of these drugs (carfilzomib
or daratumumab). Methods: Prospective analysis of data of 19 RRMM patients who progressed after multiple lines
of therapy (including bortezomib and lenalidomide/pomalidomide) and had suboptimal
response/stable/progressive disease after receiving carfilzomib or daratumumab based
combination as last therapy. All patients received combination of carfilzomib plus
daratumumab along with dexamethasone (DKd) after prior consent. Daratumumab (16 mg/kg
IV) was administered weekly (days 1, 8, 15, and 22) during cycles 1 and 2, every 2
weeks (days 1 and 15) during cycles 3–6, and every 4 weeks thereafter. Carfilzomib
was administered weekly on days 1, 8, and 15 of each 28-day cycle. Patients received
an initial carfilzomib dose of 20 mg/m2 on day 1,2; 27 mg/m2 on day 8, 9, 15, 16 of
cycle 1, which increased to 70 mg/m2 on day 1, 8, 15 from cycle 2 onwards if deemed
tolerable. Dexamethasone was given as fixed-dose of 40 mg weekly. Results: Eighteen of 19 patients (including 3 high risk cytogenetics) to DKd (CR-4, very good
partial response-10, partial response-02). After median follow-up of 16 months, progression-free
survival (PFS) was 95%. Median PFS was not reached. Three patients who were transplant eligible
received high-dose chemotherapy followed by autologous stem-cell transplantation and
achieved minimal residual disease negativity. The most frequent all grade side effects
were hematological, which included neutropenia 30%, anemia 70%, and thrombocytopenia
42%. Most frequent non hematological side effects were nausea 40%, vomiting, cough,
respiratory tract infections, asthenia, and loss of appetite. Conclusion: Carfilzomib plus daratumumab based combination in RRMM patients has shown promising
results in phase Ib study, where patients with prior exposure to either of these drugs
were excluded. Our data show similar or better response of this combination in patients
who had progressive disease/stable disease/minimal response to either of carfilzomib
or daratumumab. This combination can be a better option in heavily treated RRMM (with
prior exposure to either of carfilzomib or daratumumab) producing deeper and durable
responses. A larger study may be required to prove this benefit.
Keywords
Carfilzomib - daratumumab - multiple myeloma - relapsed/refractory
