OBJECTIVES:

The efficacy of ponatinib as frontline treatment in patients with newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukaemia (Ph+ ALL) was assessed in MDACC, a phase II, single-centre, single-arm study of ponatinib + hyper-CVAD in adult patients, and in GIMEMA LAL1811, a phase II, multicentre, single-arm study of ponatinib + steroids in patients >60 years or unfit for intensive chemotherapy and stem cell transplant. Matching-adjusted indirect comparisons were used to compare the efficacy versus imatinib + hyper-CVAD and imatinib monotherapy.

METHODS:

National Institute for Health and Care Excellence guidelines were applied. A systematic literature review was conducted to identify comparator studies including ≥15 adults with newly diagnosed Ph+ ALL receiving imatinib. Population-adjusted hazard ratios (aHR) were calculated for overall survival (OS) and population-adjusted odds ratios (aOR) for complete molecular remission rates (CMR). Prognostic factors and effect modifiers used for cohort balancing were based on clinical expert opinion.

RESULTS:

Two studies (GRAAPH-2005 and NCT00038610) reporting the efficacy of frontline imatinib + hyper-CVAD and one reporting the efficacy of frontline imatinib monotherapy induction + imatinib-containing consolidation (ADE10) were identified. Ponatinib + hyper-CVAD prolonged survival and had a higher CMR than imatinib + hyper-CVAD (aHR [95% confidence interval (CI)] for OS = 0.35 [0.17-0.74] for MDACC vs. GRAAPH-2005 and 0.35 [0.18-0.70] for MDACC vs. NCT00038610; aOR [95% CI] for CMR = 12.11 [3.77-38.87] for MDACC vs. GRAAPH-2005 and 5.65 [2.02-15.76] for MDACC vs. NCT00038610). Similarly, ponatinib + steroids prolonged survival and had a higher CMR than imatinib monotherapy induction + imatinib-containing consolidation (aHR [95% CI] for OS = 0.24 [0.09-0.64] and aOR for CMR = 6.20 [1.60-24.00] for GIMEMA LAL1811 vs. ADE10).

CONCLUSIONS:

In adults with Ph+ ALL, frontline treatment with ponatinib is associated with better outcomes than frontline treatment with imatinib-based regimens. Results should be interpreted with caution due to known limitations of matching-adjusted indirect comparisons.