PracticeUpdate: Conference Series - EHA 2018

Nilotinib and Lower-Intensity Chemotherapy Promising Treatment for Ph+Acute Lymphoblastic Leukemia Treatment associated with a highmajor molecular response rate and positive short-termoutcome N ilotinib in combination with low- er-intensity chemotherapy appears to be a promising option to treat In intent to treat analysis, the major molec- ular response rate was 43/54 patients (80%) after cycle 2 and 38/41 patients (93%) after cycle 4. The research team categorized this outcome as “good as expected” and the trial is continuing. In total, 265 patients will be required to assess if using no cytarabine at all is feasible.

arm after cycle 4, defined as BCR-ABL1/ ABL1 ratio < 0.1% in the bone marrow, is equivalent to standard treatment. Secondary endpoints are hematologic complete remission, early mortality, progression-free survival, per protocol event-free survival and overall survival. An interim analysis was scheduled after enrollment of the first 60 patients to ensure the overall major molecular response rate did not significantly differ from the anticipated 80% rate. The current analysis focused on the initial 60 patients, randomized between March 2016 and June 2017 (M/F, 29/31; median age, 47 years; minor BCR-ABL1 breakpoint, 72%). The median follow-up period was 14 months (IQR, 11.6–16.2) and the minimal follow-up of patients who were still alive was 3.8 months. All patients but 1, who early died from a septic shock, achieved hematologic complete remission after cycle 1. During the initial 4-cycle period, 4 additional patients in complete remission discontinued the planned therapy during cycle 1 (1 septic shock, 1 chest pain, 1 par- aplegia, 1 cannabis arteritis) and 1 during cycle 3 (prolonged cytopenia).

adult patients with Philadelphia chromo- some-positive (Ph+) acute lymphoblastic leukemia (ALL). The treatment combination is associated with a high major molecular response rate and a positive short-term outcome, the research team, led by Yves Chalandon, MD, Head of the Oncology Hematology and Allogeneic Hematopoietic Stem Cells Unit at Geneva University Hospitals in Switzerland, said in their abstract. Although Ph+ ALL is a relatively uncom- mon disease, it accounts for approximately 20% to 30% of adults diagnosed with ALL and is the most common cytogenetic abnormality in adult patients with this disease. Compared with Ph-negative ALL, Ph+ ALL has been found to have a poorer prognosis. The use of tyrosine kinase inhibitors (TKIs) to treat patients with Ph+ ALL has resulted in the need for a lower intensity of chemo- therapy to treat the disease. The study investigators previously reported on a randomized GRAAPH-2005 trial with imati- nib that identified better short-term results when patients received lower-intensity chemotherapy during the first treatment cycle (Y. Chalandon et al, Blood 2015). In the current study, part of the ongoing GRAAPH-2014 trial with nilotinib, the researchers conducted a random evalu- ation of reducing chemotherapy intensity by omitting high-dose cytarabine during the second treatment cycle. They also repeated cycles 1 and 2 for a total of 4 cycles to prolong TKI exposure and reach a deeper response prior to allogeneic or autologous stem cell transplantation in these patients. For the purposes of the study, patients 18 to 59 years old with newly diagnosed previously untreated de novo Ph+ ALL and an ECOG-PS ≤ 3 are eligible for ran- domization following a steroid prephase. The primary determinant of effectiveness is confirming that the major BCR-ABL1 molecular response in the no-cytarabine

At the time of the current analysis, the researchers noted, 31 and 13 patients had received allogeneic and autologous stem cell transplants in the first complete remis- sion, respectively (transplant rate, 73%). Seven out of these 59 patients relapsed, however, (including 4 post-transplant relapses) and 3 patients died (including 2 deaths in complete remission, 1 of which occurred after a stem cell transplant). At the 1-year mark, progression-free survival and overall survival were esti- mated at 84.5% (95% CI 75.0–95.2) and 95.9% (95% CI 90.3–100), respectively. The researchers determined that when initiation of unplanned therapies prior to transplants was considered an event (3 dasatinib, 1 imatinib), per protocol event- free survival was estimated at 79.7% (95% CI 69.5–91.4) after 12 months.

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EHA 2018 • PRACTICEUPDATE CONFERENCE SERIES