HSCT after quizartinib or chemotherapy extends OS in AML subset
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ORLANDO — Hematopoietic stem cell transplantation after treatment with quizartinib or salvage chemotherapy extended survival among patients with FLT-internal tandem duplication-mutated relapsed or refractory acute myeloid leukemia, according to post-hoc analyses of the randomized QuANTUM-R study presented at TCT | Transplantation & Cellular Therapy Meetings.
Participants in the trial who achieved composite complete remission prior to allogeneic HSCT also survived longer.
“The treatment effect with quizartinib, with censoring at the time of transplant, was consistent with the overall positive treatment effect observed with quizartinib [compared with] salvage chemotherapy in patients with [this disease],” Siddhartha Ganguly, MD, FACP, professor of medicine and deputy director of hematologic and cellular therapies at University of Kansas Medical Center, said during the presentation. “Quizartinib continuation after HSCT appears to be associated with better survival outcomes and is tolerable.”
Results of the QuANTUM-R study showed quizartinib (Daiichi Sankyo) — a once-daily, selective oral FLT3 inhibitor — conferred an OS benefit compared with salvage chemotherapy (median, 6.2 vs. 4.7 months; HR = 0.76; 95% CI, 0.58-0.98) among 367 patients with relapsed or refractory AML who harbored FLT-ITD mutations.
Ganguly and colleagues conducted post-hoc analyses of participants who underwent subsequent HSCT, including 85 patients who received quizartinib and 19 who received salvage chemotherapy.
Eighty-four patients in the quizartinib group underwent allogeneic HSCT and one underwent autologous HSCT. Six patients in the quizartinib group who underwent allogeneic HSCT and five patients in the salvage chemotherapy group received additional AML therapy.
Patients in the quizartinib group had the option of resuming treatment with quizartinib 30 to 100 days after HSCT per investigator discretion or institutional policy.
An analysis of pooled data from QuANTUM-R included 104 patients who underwent any HSCT and 263 patients who did not undergo transplantation. Results showed those who underwent HSCT achieved longer median OS (12.2 months vs. 4.4 months, P < .0001) and were more likely to survive 1 year (50% vs. 13%).
Pooled data also showed superior median OS among patients with composite complete remission as the last recorded response before allogeneic HSCT compared with those who did not achieve such a response (20.1 months vs. 8.8 months).
Patients achieved longer OS with vs. without HSCT regardless of whether they received quizartinib (median, 11.9 months vs. 4.5 months; 1-year OS rate, 50% vs. 13%) or salvage chemotherapy (12.7 months vs. 4 months; 1-year OS rate, 51% vs. 12%).
Patients in the quizartinib group who achieved composite complete remission and resumed quizartinib after allogeneic HSCT achieved longer median OS than those with the same response who did not resume quizartinib (27.1 months vs. 5.4 months). Median time from allogeneic HSCT to quizartinib resumption was 65 days among the 48 patients who resumed therapy.
Four patients in the quizartinib group died less than 30 days after allogeneic HSCT.
As of data cutoff in February 2018, 48 of 78 patients (59%) in the quizartinib group and nine of 14 patients (64%) in the chemotherapy group who underwent allogeneic HSCT without additional AML therapy died, primarily due to disease progression.
Resumption of quizartinib after allogeneic HSCT did not appear associated with increased rates of treatment-related adverse events.
“These data illustrate the value of using continued quizartinib treatment to target the FLT3-ITD mutation in these patients,” Ganguly said. “This is an ad-hoc analysis, and we don’t have the data on individual patients’ post-transplant conditions or outcome and potential graft-versus-host-disease, among other things. If we can combine all these data with our data, I imagine we will be publishing another abstract next year.” – by John DeRosier
Reference:
Ganguly S, et al. Abstract 7. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.
Disclosures:
Ganguly reports research funding from Daiichi Sankyo, consultant/advisory board roles with and honoraria from Kite Pharma, and a speakers bureau role with and honoraria from Seattle Genetics. Please see the abstract for all other authors’ relevant financial disclosures.
Perspective
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Bart Scott , MD
The major limitation of this study is that it was for patients who had not received prior FLT3-ITD inhibitor therapy. The problem with this data set is that I don’t think it represents current care, which is upfront FLT3 inhibitor therapy.
The real question is whether quizartinib is beneficial for patients with FLT3 mutations who have been exposed to FLT3 inhibitors.
Are there still clinical benefits that can be taken from this study? Probably. I think it’s a more specific drug with a lower toxicity profile, but there is a difference between saying ‘probably’ and knowing if there is a clinical benefit.
The maintenance issue was very interesting and compelling but, again, there are limitations because these patients were not exposed to FLT3 inhibitors upfront. At least in that subset of patients, there was a benefit in giving quizartinib maintenance, which shows that maintenance therapy as a whole could be effective.
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