Edward D. Agura M.D.

Kim, H. T., K. W. Ahn, Z. H. Hu, M. S. Davids, V. O. Volpe, J. H. Antin, M. L. Sorror, M. Shadman, O. Press, J. Pidala, W. Hogan, R. Negrin, S. Devine, J. Uberti, E. Agura . . . and J. R. Brown (2019). “Prognostic Score and Cytogenetic Risk Classification for Chronic Lymphocytic Leukemia Patients: Center for International Blood and Marrow Transplant Research Report.” Clin Cancer Res Jun 28. [Epub ahead of print].

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Purpose: To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT).Experimental Design: We performed a retrospective analysis of outcomes of 606 patients with CLL who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research.Results: On the basis of multivariable models, disease status, comorbidity index, lymphocyte count, and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low-, intermediate-, high-, and very-high-risk [4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, P < 0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, P < 0.0001]. We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or >/=5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (P < 0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4 years) and OS (75% at 4 years).Conclusions: In this large cohort of patients with previously treated CLL who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic-based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.

Moskowitz, C. H., J. Walewski, A. Nademanee, T. Masszi, E. Agura, J. Holowiecki, M. H. Abidi, A. I. Chen, P. Stiff, S. Viviani, V. Bachanova, A. Sureda, T. McClendon, C. Lee, J. Lisano and J. Sweetenham (2018). “Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse.” Blood 132(25): 2639-2642.

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The phase 3 AETHERA trial established brentuximab vedotin (BV) as a consolidative treatment option for adult patients with classical Hodgkin lymphoma (cHL) at high risk of relapse or progression after autologous hematopoietic stem-cell transplantation (auto-HSCT). Results showed that BV significantly improved progression-free survival (PFS) vs placebo plus best supportive care alone. At 5-year follow-up, BV continued to provide patients with sustained PFS benefit; 5-year PFS was 59% (95% confidence interval [CI], 51-66) with BV vs 41% (95% CI, 33-49) with placebo (hazard ratio [HR], 0.521; 95% CI, 0.379-0.717). Similarly, patients with >/=2 risk factors in the BV arm experienced significantly higher PFS at 5 years than patients in the placebo arm (HR, 0.424; 95% CI, 0.302-0.596). Upfront consolidation with BV significantly delayed time to second subsequent therapy, an indicator of ongoing disease control, vs placebo. Peripheral neuropathy, the most common adverse event in patients receiving BV, continued to improve and/or resolve in 90% of patients. In summary, consolidation with BV in adult patients with cHL at high risk of relapse or progression after auto-HSCT confers a sustained PFS benefit and is safe and well tolerated. Physicians should consider each patient’s HL risk factor profile when making treatment decisions. This trial was registered at www.clinicaltrials.gov as #NCT01100502.

Moskowitz, C. H., J. Walewski, A. Nademanee, T. Masszi, E. Agura, J. Holowiecki, M. H. Abidi, A. I. Chen, P. Stiff, S. Viviani, V. Bachanova, A. Sureda, T. McClendon, C. Lee, J. Lisano and J. Sweetenham (2018). “Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse.” Blood Sep 28. [Epub ahead of print].

Full text of this article.

The phase 3 AETHERA trial established brentuximab vedotin (BV) as a consolidative treatment option for adult patients with classical Hodgkin lymphoma (cHL) at high risk of relapse or progression following autologous hematopoietic stem cell transplant (auto-HSCT). Results showed that BV significantly improved progression-free survival (PFS) versus placebo plus best supportive care alone. At 5 years follow-up, BV continued to provide patients with sustained PFS benefit; 5-year PFS was 59% (95% CI 51-66) with BV versus 41% (95% CI 33-49) with placebo (HR 0.521, 95% CI, 0.379-0.717). Similarly, patients with >/= 2 risk factors on the BV arm experienced significantly higher PFS at 5 years than patients in the placebo arm (HR 0.424, 95% CI 0.302-0.596). Upfront consolidation with BV significantly delayed time to second subsequent therapy, an indicator of ongoing disease control, versus placebo. Peripheral neuropathy, the most common adverse event in patients receiving BV, continued to improve and/or resolve in 90% of patients. In summary, consolidation with BV in adult patients with cHL at high risk of relapse or progression after auto-HSCT confers a sustained PFS benefit and is safe and well tolerated. Physicians should consider each patients’ HL risk factor profile when making treatment decisions. (www.clinicaltrials.gov #NCT01100502).