To date, OPTIMISMM is the only phase 3 study in early RRMM to report a significantly and clinically meaningful PFS improvement in LEN-exposed patients.
The lifetime risk of getting multiple myeloma is about 1 in 132. Those with advanced multiple myeloma whose disease grows worse after several lines of therapy, are left with minimal treatment options and are known to have a poor prognosis; in fact, the median survival time for these individuals is estimated to be about 9 months.
Despite the available approved antimyeloma agents, management of those with relapsed or refractory multiple myeloma (RRMM) has remained challenging.
Now, at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, researchers report promising data from a phase 3 trial comparing the use of pomalidomide, bortezomib, and low-dose dexamethasone (PVd) with bortezomib and low-dose dexamethasone (Vd) in RRMM patients who have been exposed to lenalidomide (LEN).
Pomalidomide is known as a standard-of-care treatment (Tx) for patients with RRMM, and it has been shown to demonstrate synergistic anti-myeloma activity when combined with dexamethasone (DEX) and proteasome inhibitors (PIs). This combination is indicated for those with RRMM who have received 2 or more previous Txs (including LEN and a PI).
“As LEN becomes increasingly established in up-front Tx of MM,” study authors write, “patients who have exhausted the benefit of LEN represent a clinically relevant unmet medical need.”
For their study, aptly referred to as OPTIMISMM, investigators enrolled 559 patients with RRMM; all had 1 to 3 prior Tx lines and 2 or more cycles of prior LEN. The patients were randomized 1:1 into 2 arms: those who would receive PVd (281) and those who would receive Vd (278). The primary endpoint for the study was progression-free survival (PFS).
All patients had prior LEN, with 71% LEN refractory in those to receive PVd and 69% LEN refractory in those to receive Vd; 72% compared with 73% had prior BORT; and 70% compared with 66% were refractory to last Tx, according to study authors. They added that the median prior Tx lines was 2, and 40% in the PVd arm had 1 prior Tx line, compared with 41% in the Vd arm.
In the study, the PVd arm received 4 mg of POM orally on days 1 to 14 of a 21-day cycle, in addition to 1.3 mg/m2 of bortezomib (BORT) administered subcutaneously on days 1, 4, 8, and 11 of the 21 days for cycles 1 to 8 and on days 1 and 8 of 21 days for cycle 9 and onward until disease progression, and orally, DEX 20 mg/day (10 mg/day if over 75 years of age) on days 1, 2, 4, 5, 8, 9, 11, and 12 of 21 days for cycles 1 to 8, as well as on days 1, 2, 8, and 9 of 21 days for cycles 9 and onward until disease progression.
The Vd arm received 1.3 mg/m2 of BORT administered subcutaneously on days 1, 4, 8, and 11 of 21 days for cycles 1 to 8 as well as on days 1 and 8 of 21 days for cycle 9 and onward until disease progression, along with DEX 20 mg/day (10 mg/day if over 75 years of age) orally on days 1, 2, 4, 5, 8, 9, 11, and 12 of 21 days for cycles 1 to 8 and on days 1, 2, 8, and 9 of 21 days for cycles 9 and onward until disease progression.
The investigators found that after a median follow-up of 16 months, PVd “significantly reduced the risk of progression or death” by 39% compared with Vd. However, they add that the OS data are not mature. Furthermore, neutropenia (42% vs. 9%), infections (31% vs. 18%), and thrombocytopenia (27% vs. 29%) were noted as the most common grade 3/4 treatment-associated adverse events.
“To date, OPTIMISMM is the only phase 3 study in early RRMM to report a significant and clinically meaningful PFS improvement in patients who were entirely LEN exposed and 70% LEN refractory,” the authors conclude. They add that in patients with only 1 prior Tx line, PVd showed improved benefit in this patient population.
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