Quick Poll results from the of OncoFacts 2010

If imatinib, nilotinib, and dasatinib are all approved for front-line therapy of newly diagnosed chronic phase (CP) chronic myelogenous leukemia (CML), what would you recommend as front-line therapy for a 42-year-old man who presents with high-risk CML by both the Sokal and Hasford (Euro) scoring systems and who has no matched sibling donor?

Discussion

The IRIS trial of front-line imatinib versus Ara-C plus interferon was updated at American Society of Hematology (ASH) 2009 Annual Meeting. During the eighth year of follow-up, there was 1 progression to accelerated phase (AP)/blast crisis (BC) and 2 non-CML-related deaths. Major molecular response (MMR) rates increased over the course of imatinib therapy from 24% at 6 months to 39% at 12 months to 86% of those still on treatment at 8 years. No patient with a documented MMR at 12 months progressed to AP/BC at 8 years.

The German CML Study IV was updated at the 2010 Annual Oncology Meeting. This study randomized newly diagnosed patients with CP-CML to imatinib 800 mg versus imatinib 400 mg versus imatinib 400 mg plus interferon. At 12 months and 18 months, the CCyR rates and MMR rates are as noted below. The more rapid achievement of MMR with imatinib 800 mg was noted in the Sokal low-risk and intermediate-risk patients but not in the high-risk patients.

                             CCyR                            MMR
             IM-400 IM-800 IM400-IFN    IM-400 IM-800 IM400-IFN
12 mos    49.8% 63.2% 49.5%          31.1% 55.8% 33%
18 mos    66.6% 73.8% 70%             51.5% 70.2% 54.7%CCyR, complete cytogenic response; MMR, major molecular response; IM-400; imatinib 400 mg; IM-800, imatinib 800 mg; IM400-IFN; imatinib 400 plus interferon.

The ENESTnd trial of front-line imatinib 400 mg versus nilotinib either 300 mg or 400 mg BID for newly diagnosed patients with CP-CML was initially presented at ASH 2009 and updated at the 2010 Annual Oncology Meeting. The MMR rates at 18 months were 88% for nilotinib 300 mg, 86% for nilotinib 400 mg, and 48% for imatinib 400 mg. Complete cytogenetic response (CCyR) rates for Sokal high-risk patients at 16 months for nilotinib 300 mg, nilotinib 400mg, and imatinib 400 mg were 85%, 82% and 75%, respectively.

In the DASISION trial, imatinib 400 mg was compared to dasatinib 100 mg as front-line therapy for newly diagnosed CP-CML. Complete cytogenetic response and MMR rates at 12 months for imatinib were 72% and 28% versus 83% and 46% for dasatinib.

References

1. Deininger M, O’Brien SG, Guilhot F, et al. International randomized study of interferon vs STI571 (IRIS) 8-year follow up: Sustained survival and low risk for progression or events in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib. Blood. 2009;114(22). Abstract 1126.
2. Hehlmann R, Lauseker M, Jung-Munkwitz S, et al. Treatment optimization by high-dose imatinib: Randomized comparison of imatinib 800 mg versus imatinib 400 mg ± IFN in newly diagnosed BCR-ABL positive chronic phase (CP) CML: The German CML-study IV. J Clin Oncol. 2010;28(15s). Abstract 6517.
3. Larson RA, le courte PD, Reiffers J, et al. Comparison of nilotinib and imatinib in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP): ENESTnd beyond one year. J Clin Oncol. 2010;28(15s). Abstract 6501.
4. Kantarjian H, Shah NP, Hocchaus A, et al. Dasatinib compared to imatinib (IM) in patients (pts) with newly diagnosed chronic-phase chronic myelogenous leukemia in chronic phase (CML-CP): Twelve-month efficacy and safety from the phase III DASISION study. J Clin Oncol. 2010;28(15s). Abstract LBA6500.

 

* The aggregate results from this question were compiled from the responses submitted by oncologists who participated in the OncoFacts Quick Poll monthly question.