Program: Oral and Poster Abstracts
Session: 653. Myeloma: Therapy, excluding Transplantation: Poster I
Methods: In the phase I portion, the primary endpoint is to determine the maximum tolerated dose (MTD) of the combination. Key eligibility criteria are relapsed or refractory disease but not progressed on Len 25 mg; ≥2 prior lines of therapy, absolute neutrophil count ≥ 1000/µL; Platelets ≥60,000/µL; and creatinine clearance of ≥ 40ml/min. Patients are treated with escalating doses of MDV9300 and Len utilizing a 3x3 escalation design (Table 1). If stable disease is the best response after 4 cycles, patients have the option of adding dexamethasone (20-40mg weekly). Len dose may be modified independently of MDV9300. Patients can receive a maximum of 12 cycles of therapy.
Results: Twelve patients are evaluable to date. The median age was 68.5 (range 49–82) and the median time from diagnosis 4.98 years (range 1.54–12.62). At study entry, 67% had high risk cytogenetics (del 17p, complex karyotype, gain 1q) and the median number of prior treatment lines was 2 (range 2-11). 100% of patients had received prior Len, bortezomib and Dex, 50% alkylating agents (cyclophosphamide, oral melphalan, bendamustine), 75% autologous stem cell transplant, 25% pomalidomide and 33% carfilzomib. MDV9300 infusion has been well tolerated with only one grade 2 infusion related toxicity with sore throat. The patient received hydrocortisone with no further reaction observed. Grade 3/4 Anemia, neutropenia, and thrombocytopenia attributable to therapy have been seen in 25%, 23%, and 34% of patients, respectively. Other common grade 2-3 therapy related adverse events are fatigue (50%), anorexia (17%), and hypophosphatemia (17%). There has been no grade 3 or higher infection and no worsening of neuropathy from baseline. Len dose was reduced in 3 patients (25%) and increased in one. There has been no dose reduction in MDV9300. Dex 20 mg or less was added in 2 patients for muscle cramps and < PR after 3 cycles. To date 7 patients are off therapy; 1 due to grade 3 fatigue and 6 due to disease progression. Five patients continue on therapy at respective 12, 11, 9, 5 and 3 months. Responses to date have been 3 Very good partial response,1 partial response, 2 minimal response and 2 stable disease.
Conclusion: The combination of steroid sparing MDV9300 and Len regimen has demonstrated an acceptable toxicity profile to date with evidence of anti-myeloma activity. This is the first reported combination anti-PD-1 based immune therapy for MM. Updated results will be presented at the meeting including the MTD dose for phase II.
Table 1
|
MDV9300- mg/kg Intravenously given on day 3 every 28 days |
Lenalidomide- mg orally days 1-21 every 28 days
|
DLT Evaluable |
DLTs |
Cohort 1 |
1.5 |
15 |
6 |
Grade 3 fatigue. Cohort extended to 6 |
Cohort 2 |
3 |
15 |
3 |
none |
Cohort 3 |
3 |
25 |
3 |
none |
Cohort 4 |
6 |
25 |
0 |
|
Acknowledgements: Drug has been provided by Medivation; The study is sponsored by the American Cancer Society
Disclosures: Efebera: Regimmune: Research Funding . Avigan: Regimmune: Research Funding .
See more of: Myeloma: Therapy, excluding Transplantation
See more of: Oral and Poster Abstracts
*signifies non-member of ASH