PB2122 VELCADITO. A PHASE II TRIAL WITH LOW DOSES OF BORTEZOMIB PLUS MELPHALAN AND PREDNISONE FOR ELDERLY PATIENTS (>75Y) WITH NEWLY DIAGNOSED MULTIPLE MYELOMA
Authors: Persona E. Pérez , Ormategui I. Oiartzabal , Angulo R. Diez , Cilaurren A. Unamunzaga , Salinas I. M. Parra , Lopez A. Santamaría , Palomares L. Cuevas , Robles de Castro D. , de Miguel Sánchez C. , Jalón M. Gabilondo , Herrero C. Pisón , Navarro G. A. Mendez , Vega González de Viñaspre A. , Guinea de Castro J. M. 
Published: June 2019

Background:

VISTA trial (bortezomib, melphalan and prednisone) is a widely used scheme for the management of patients with multiple myeloma (MM) not candidates for autologous transplant (NCMM). Original biweekly dose of bortezomib has commonly been reduced to weekly administration to improve neuropathic toxicity without compromising efficacy. Nevertheless, efficacy and toxicity data come from clinical trials, with highly selected patients. NCMM real‐life patients are older with comorbidities. Besides biology status, difficulties to get to the follow‐up visits and day care hospital for treatment, is a frequent problem.

Aims:

We conduct a clinical trial for real life patients with NCMM with reduced doses of bortezomib in order to improve neuropatic toxicity and patient comfort. The objective was to assess the efficacy and safety of a reduced‐dose scheme of bortezomib, along with melphalan and prednisone for the treatment of patients with MM over 75 years of age.

Methods

Velcadito is a phase II trial with dose reduction of bortezomib, consisting on a first cycle with bortezomib (1.3 mg/m2) days 1, 4, 8 and 11, followed by bortezomib (1.0 mg/m2) days 1 and 4 from cycle 2 and beyond. Melphalan 9 mg/m2 and prednisone 60 mg/m2 were administered in all cycles on days 1 and 4, every 28 days. At minimum of 8 cycles of treatment were planned, for patients not in complete remission (CR) after 8 cycles the treatment could be continued, at physician discretion.

Results:

From April 2015 to May 2017, 23 patients with newly diagnosed NCMM were included. Main characteristics of the patients are detailed in table 1. It should be noted that 72.5% had a creatinine clearance of < 60 ml/min, at diagnosis. 13% of patients were considered high‐risk by cytogenetics. Response: response rate (RR) was 65% (26% CR), 3 out of 6 patients in CR were analyzed for minimal residual disease (MRD), all of them had MRD negative with a sensitivity of 10−4. With a median follow‐up of 23 months (16‐44), PFS was 21 months (figure 1A), and median OS has not been achieved (figure 1B). Three patients started a second line of treatment because of lack of response but without progression, so time to next treatment was 17 months. Toxicity: The most frequent grade III‐IV adverse effects (AE) were: infections (48%), thrombocytopenia (39%) and neutropenia (30%). Neurological toxicity was mild: 35% any grade (1% grade III‐IV). Remaining toxicity was mostly grade I‐II. Patients with reduced or withdrawal doses were respectively: bortezomib: 8% and 17%; melphalan: 43% and 30%, and prednisone: 13% and 17%. At the time of analysis 8 patients had died (1 with CR, 5 with active disease and 2 with progressive disease).

Summary/Conclusion:

Velcadito scheme is an adapted treatment for elderly patient with NCMM, with favorable neurological and extra‐hematologic toxicity profile and comparable efficacy to VISTA trial. However, hematological toxicity caused by melphalan is high, with frequent dose adjustment needs and withdrawal. It could represent an alternative treatment for real life NCMM patients with reduce visit to day care hospital, comfortable administration, although, results may be interpreted with caution due to low recruitment.

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