Improved outcomes, but still substantial part experiences relapses

Chemotherapy-based approaches still constitute an essential feature in the treatment paradigm of adult acute lymphoblastic leukaemia (ALL). The German Multicenter Study Group for adult ALL (GMALL) is a well-established and commonly used protocol for ALL [1]. Over the years, new versions of the protocol have been developed aiming to improve patient outcomes [2]. While results indeed improved, a substantial patient segment still experienced relapses. This was concluded from a retrospective analysis including all adult ALL patients (n=81) who were treated with GMALL in Sheba Medical Center (Israel) between 2008 and 2020 [3].

Included patients had a median age of 36 years (range 18-73); 36% were adolescents and young adults. In total, 43 patients (53%) had B-cell ALL (B-ALL), 12 (15%) had Philadelphia chromosome-positive ALL, and 26 (32%) had T-cell ALL (T-ALL). Treatment for 55 patients consisted of allogeneic stem cell transplantation using matched sibling (47%), matched unrelated (31%), haploidentical (7%), partially mismatched (12%), and cord blood donors (3%).

A first remission was attained by 70 patients (88%), 4 (5%) died during the first 2 induction phases. The 2-year overall survival (OS) rate was 62% and the 5-year OS rate was 44%. Estimated 2- and 5-year leukaemia-free survival rates were 52% and 35%, respectively. Overall, disease relapse (31%), lethal infection (28%), and graft-versus-host disease (14%) accounted for most patient deaths. Of patients achieving first remission, 20 (29%) eventually relapsed after a median time of 9.8 months (range 1.1-69.3). Of 50 transplanted patients attaining first remission, 15 (30%) relapsed after a median time of 10.9 months (range 3.8-32.8).

Concerning OS, multivariate analysis revealed that increasing patient age (HR 1.026; P=0.035) as well as a higher number of clones detected with baseline cytogenetic analysis (HR 2.69; P=0.0002) were associated with inferior outcome. T-ALL patients experienced longer survival compared with B-ALL (87 vs 56 months; P=0.019). Patients transplanted using cord blood donors had inferior survival compared with transplants using matched sibling donors and fully matched unrelated donors (12.8, 71.3, and 73.4 months, respectively). Relapse-free survival was significantly better in patients with T-ALL compared with B-ALL (90 vs 50 months; P=0.039).

According to Dr Danielle Fredman (Sheba Medical Center, Israel), it is conceivable that, in the near future, novel therapeutic modalities for adult ALL involving the use of monoclonal antibodies and CAR T-cell therapy will help reduce relapse rates and further improve the current outcomes of patients treated on the GMALL protocol.

1. Gökbuget N, et al. Blood. 2012 Aug 30;120(9):1868-76.
2. Apel A, et al. Isr Med Assoc J. 2014;16:224-8.
3. Fredman D, et al. Evaluating Outcomes of Adult Patients with Acute Lymphoblastic Leukemia Treated on the GMALL Protocol. 62^nd ASH Annual Meeting, 5-8 December 2020. Abstract 982.

Posted on 18 February 202122 February 2021