[157] Phase III Trial of Immunotherapy with Recombinant Interleukin-2 (rIL-2) Versus Observation in Patients < 60 Years with Acute Myeloid Leukemia (AML) in First Remission (CR1): Preliminary Results from Cancer and Leukemia Group B (CALGB) 19808. Session Type: Oral Session

Jonathan E. Kolitz, Vera Hars, Daniel J. DeAngelo, Steven L. Allen, Thomas C. Shea, Ravi Vij, Eva Hoke, Clara D. Bloomfield, Michael A. Caligiuri, Stephen L. George, Richard A. Larson Cancer and Leukemia Group B, Chicago, IL, USA

The CALGB evaluated the use of rIL-2 for immunotherapy of minimal residual disease in a phase III trial in patients with AML in first CR after completing all planned chemotherapy. The rationale supporting the use of rIL-2 in this setting includes its ability to effect antigen-independent cytotoxicity against AML blasts, its non-cross resistance with cytotoxic agents, and its ability to expand cytotoxic T and natural killer (NK) cells. Pts < 60 years with untreated non-M3 AML were eligible. 734 patients were enrolled. The first 302 patients were randomized between 2 induction regimens: Ara-C, Daunorubicin, and Etoposide (ADE) or ADEP with the P-glycoprotein modulator PSC-833 (Kolitz et al, ASH 2005). The remaining 432 patients received ADE induction. Post-remission therapy was based on cytogenetic risk factors: patients with Core Binding Factor (CBF) AML received 3 courses of High-Dose Ara-C (HiDAC), while all others were assigned to receive a 2 step autologous transplant (ASCT) regimen (Linker et al, Biol Blood Marrow Transpl 2000). Randomization between rIL-2 and observation was to occur no later than 120 days after day 1 of the last HiDAC cycle or day 0 of ASCT, as soon as the neutrophil count > 750/l, platelets > 50,000/l with bone marrow showing a leukemia-free state and trilineage maturation and recovery from non-hematological toxicity to < grade 2. The 90 day immunotherapy regimen consisted of low-dose rIL-2 sequences for expanding cytotoxic effector cells and brief, higher dose bolus treatments aimed at activating them. rIL-2 was given SC at 1 x 10⁶ IU/m² on days 1-14, 19-28, 33-42, 47-56, 61-70 and 75-90, and 12-15 x 10⁶ IU/m² on days 15-17, 29-31, 43-45, 57-59 and 71-73. CR was achieved in 77% of evaluable patients. After HiDAC consolidation or ASCT, patient refusal, early relapse, and delayed blood count recovery accounted for nearly all failures to undergo randomization to IL-2 or observation. The distribution of patients with CBF and non-CBF AML was comparable between the randomized arms. The median follow-up time from the post-remission randomization date for the surviving patients is 29 months. By intention-to-treat, for the 214 randomized patients, the 3-year disease-free survival rate is 45% (95% CI: 35%,56%) on the observation arm and 56% (47%,67%) on the rIL-2 arm (p=0.11; logrank test); the 3-year overall survival rate is 61% (52%,72%) for patients randomized to observation and 68% (58%,79%) for the rIL-2 arm (p=.0.09). Twenty-nine of the 107 patients randomized to rIL-2 therapy either refused to receive rIL-2 or were unable to start because of unresolved toxicities; another 28 patients started treatment but failed to complete their 90-day course. Grade 4 toxicities were neutropenia (17%), thrombocytopenia (11%), febrile neutropenia (FN, 1%), increased bilirubin (1%) and hypocalcemia (1%). Grade 3 toxicities, observed in 10%-14% of patients, were hypotension, fatigue, dehydration and FN. We conclude that post-consolidation immunotherapy with 90 days of rIL-2 is tolerable but not well accepted by patients and/or physicians. Further follow-up and additional analyses are planned, correlating outcomes with clinical subsets, amount of rIL-2 therapy received, as well as measurements of ex vivo cytotoxicity mediated by patients effector cells against cryopreserved autologous AML blasts.
Abstract #157 appears in Blood, Volume 110, issue 11, November 16, 2007
Keywords: Acute Myeloid Leukemia|Immunotherapy|Phase III
Disclosure: Off Label Use: Investigational use of recombinant interleukin-2 for treatment of patients with acute myeloid leukemia in first complete remission.

Monday, December 10, 2007 7:30 AM

Session Info:  Simultaneous Session: Acute Myeloid Leukemias: Therapy, excluding Transplantation-Immunotherapeutic Approaches (7:30 a.m.-9:00 a.m.)