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A phase I/II study (NCT01541332) of pomalidomide (POM), dexamethasone (DEX), and pegylated liposomal doxorubicin (PLD) for patients with relapsed/refractory (R/R) multiple myeloma (MM).
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
Background: POM is a newer IMiD immunomodulatory compound with high in vitro potency that has shown promise in combination with DEX as an effective treatment option for R/R MM patients (pts), even those refractory to bortezomib and lenalidomide (LEN). We conducted a phase I/II trial investigating the safety and efficacy of POM in combination with IV DEX and PLD using a modified dose and longer 28-day schedule in R/R MM pts. Methods: Phase I pts had progressive MM at the time of enrollment that was R/R to at least one anti-MM regimen. Phase II pts had to be refractory to LEN (singe-agent or in combination) demonstrated by progressive disease while receiving LEN or relapse within 8 weeks of its last dose. During phase I, POM was administered orally at 2, 3, or 4 mg daily in 3 successive cohorts of 3 pts each on days 1-21 of each 28-day cycle. DEX was administered IV at 40 mg over 30 min and PLD was administered at 5 mg/m2as an IV infusion over 30-90 min on days 1, 4, 8, and 11 of each cycle. POM doses were escalated until maximum tolerated dose (MTD) was reached. Once MTD was reached, all subsequent pts were enrolled at that dose. Results: To date, 27 pts have been enrolled, with 18 evaluable for efficacy and 19 for safety. Pts received a median of 5 prior treatments (range, 1-18) with a median of 1 prior PLD regimens (range, 0-2). Pts have completed a median of 1 cycle (range: 0-8) with a median of 1.4 months of follow up (range: 0-7.1). No DLTs were seen during phase I, which established the MTD at 4 mg. Phase II has enrolled 16 pts at 4 mg so far. Clinical benefit was seen in 7 (39%) of evaluable pts (partial response = 22%; minor response = 17%) with another 44% showing stable disease. Common ≥ G3 adverse events included leukopenia (32% of pts), neutropenia (32%), lymphopenia (26%), and hyponatremia (16%). Neutropenia at ≥ G3 occurred in more than half of patients on the phase II trial (4 mg POM). Conclusions: The combination of pomalidomide with dexamethasone and PLD on a 28-day cycle shows efficacy for R/R MM pts. However, because of excessive ≥ G3 neutropenia, POM is being reduced to 3 mg for newly enrolled patients. Clinical trial information: NCT01541332.