PB2163 CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE “ON DEMAND” IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: REAL LIFE EXPERIENCE AND NEW PERSPECTIVES ON DOSE‐DENSE CHEMOTHERAPY
Authors: Giordano A. , Giordano C. , Pugliese N. , Piccolo G. , Cappuccio I. , Calabrò M. , Catalano L. , Pane F. 
Published: June 2019

Background:

The natural history of Multiple Myeloma (MM) is characterized by improved survival rates but relapses are still common, thus new therapeutic approaches are still needed.

Carfilzomib (K) is a selective and irreversible epoxyketone proteasome inhibitor approved in combination with dexamethasone (d) and lenalidomide (R) for the treatment of patients with relapsed‐refractory MM (1–3 previous lines of therapy) and as a single agent for the treatment of patients with relapsed or refractory MM (1 or more previous lines of therapy).

Aims:

The aim of this study is to describe the real life of our patients treated with KRd and to give new perspectives on dose‐dense chemotherapy.

Methods

Data from patients with relapsed/refractory MM treated with KRD in the Federico II University of Naples, were retrospectively analyzed.

Response was evaluated according to International Myeloma Working Group Uniform Response Criteria. Disease assessments were performed on day 1 of each cycle. In patients that had obtained a PR, VGPR, CR in at least 3 consecutive measurements carried out at monthly intervals during treatment the therapy was discontinued and the patients were reassessed every 30 days. The same treatment was reintroduced when disease progressed according to clinical and/or biochemical parameters. Finally, a different line of therapy was employed when signs of disease resistance to KRd appeared.

KRd treated patients were than divided into three cohorts as per chemotherapy dose‐density: in the first group patients received ≤50% of the expected cycles (low‐dose); in the second group patients received a dose comprised between 50% and 75% of the expected cycles (int‐dose); in the third group ≥75% of the expected cycles (high‐dose) was employed.

The primary endpoint was the time to next treatment (TTNT) for the entire population and among the three dose dense cohorts.

Secondary endpoint was the overall response rate (ORR).

Results:

From January 2016 to January 2019 forty‐two patients with a diagnosis of MM treated with KRD combination, relapsed after a previous therapy (1‐7) including bortezomib and Immunomodulatory Drugs (IMiDS), were enrolled. Median age was 63.2 years; Performance status was >2 in the 40% patients. Patients with high cytogenetic risk were the ones treated with more than two previous chemotherapy lines. All patients with more than two previous lines had received IMIDs, while these drugs weren’t employed in the 40% of those previously treated with only one line. Bortezomib was employed in almost all patients. TTNT was 13 (range 1‐30) months for the entire cohort while the median TTNT for low‐dose cohort was not reached; the int‐dose and the high‐dose cohort had a median TTNT of 13 and 5 months respectively (figure). The ORR of the entire cohort was 95%.

Summary/Conclusion:

This retrospective analysis indicates that KRd improved the outcome of patients in first relapse, of patients with ≥ 2 previous lines of therapy and of those refractory to bortezomib and IMiDS.

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Although therapies for relapsed MM are licensed as continuous treatment until progression, our data suggest that less dose‐density appears to have the same efficacy of continuous treatments but with less toxicity and significant economic savings.