Comparative Analysis of Donor and Conditioning Intensity in the MRD and Ptcy Era in Philadelphia + Acute Lymphoblastic Leukemia (Ph+ ALL). a 12-Year Span Report of 119 Center CIBMTR Report

Introduction

Recently reclassified as standard-risk, Philadelphia positive acute lymphoblastic leukemia (Ph+ ALL) had been considered a grave diagnosis prior to the advent of novel introduction of bispecific therapies and tyrosine kinase inhibitors (TKIs). Additionally, the role of minimal residual disease has been proven to be validated in the era of multiparametric flow cytometry, next-generation sequencing (NGS) , and quantitative reverse transcription polymerase chain reaction (RT-qPCR).[1],[2],[3] Given the recent advances in allogeneic transplantation risk for treatment related mortality through the advent of post-transplantation cyclophosphamide, an updated review of patient survival in MRD negative pre-transplant for pH+ ALL warrants investigation. Here, we review survival outcomes stratified by GVHD prophylaxis, conditioning intensity, and donor type in the MRD negative CR1 PH+ ALL patient population.

Methods

In this retrospective cohort study, we included MRD negative CR1 adult patients who underwent transplantation at a US-based center between 2008 and 2020. A total of 1110 patients from 119 transplant centers were identified. Pre-transplant descriptive statistics as well as subgroup univariate analysis of overall survival were provided.

Results

Of the 1110 patients identified, the median age at transplant was 48.0 (18.0-75.0) with 246 (22.2%) of patients receiving transplant at age 59 or greater. 584 (52.6%) of patients were male, 526 (47.4%) of patients were female. The median follow-up in months was 62.9 (3.0-172.7).

Donor types included 403 (36.3%) HLA identical sibling (MSD), haploidentical 146 (13.2%), HLA matched unrelated donor (MUD) 458 (41.3%), and HLA mismatched unrelated donor (MMUD) 103 (9.3%). Overall survival (OS) stratified by donor type. At 1 year, the OS was 83.8% (range 80.1-87.2%) in MSD, 89.7% (range 84.3-94.1%) in haploidentical, 80.3% (range 76.6-83.8%) in MUD, and 76.6% (range 68-84.2%) in MMUD. At 2 years, OS of 74.6 (70.2-78.7)% in MSD, 84.2 (77.8-89.6)% in haploidentical, 72.4% (range 68.2-76.4%), in MUD and 65.8% (range 56.4-74.6%) in MMUD. The 3 year OS was 71.5% (range 67-75.8%) in MSD, 79.1% (range 72.1-85.4%) in haploidentical, 68.4% (range 64.1-72.6%) in MUD, and 59.9 % (range 50.2-69.1%) in MMUD donors. (95% CI; p-value 0.034).

Post-transplant cyclophosphamide (PTCy) data was included in 671 of patients, with 432 patients stratified to no PTCy and 239 receiving PTCy. Subgroup analysis of PTCy use revealed a 1 year OS of 84.5% (range 80.9-87.7%) and 89.1% (range 84.8-92.7%) for no PTCy and PTCy use respectively. The 2-year OS was 76.3% (range 72.2-80.2%) and 81.8% (range 76.7-86.5%) for no PTCy and PTCy use respectively. The 3-year OS was 71.1% (range 66.7-75.3%) and 77.4% (range 71.9-82.6%) for no PTCy and PTCy use respectively. (95% CI; p-value 0.09).

Conditioning intensity data was included for 709 patients and were stratified by myeloablative conditioning (MAC) in 451 patients and reduced intensity and non myeloablative (RIC/NST) in 258 patients (RIC/NST). Subgroup analysis by conditioning regimen revealed a 1 year OS of 88.2% (range 85.1-91.0%) and 82.0% (range 77.1-86.5%) in MAC and RIC/NST respectively. The 2 year OS was 79.5% (range 75.1-83.1%) and 75.4 (range 69.9-80.4%) in MAC and RIC/NST respectively. And the3 year OS was 74.6% (range 70.5-78.6%) and 70.9% (range 65.2-76.3%) in MAC and RIC/NST respectively. (95% CI; p-value 0.107).

Conclusion:

We found consistent OS benefits to those in the MAC conditioning subgroup, haploidentical related donor, and PTCy subgroups as compared to individuals who received alternative treatments. Prospective trials would be required to validate these retrospective findings for patients with MRD negative Ph+ ALL in CR1.

The data presented here are preliminary and were obtained from the Statistical Center of the Center for International Blood and Marrow Transplant Research. The analysis has not been reviewed or approved by the Advisory or Scientific Committees of the CIBMTR.' The data may not be published without the approval of the Advisory Committees.

[1] Jabbour et al., “The Evolution of Acute Lymphoblastic Leukemia Research and Therapy at MD Anderson over Four Decades.”

[2] Paietta et al., “Molecular Classification Improves Risk Assessment in Adult BCR-ABL1–Negative B-ALL.”

[3] Liu-Dumlao et al., “Philadelphia-Positive Acute Lymphoblastic Leukemia.”