PracticeUpdate Oncology Best of 2018

TOP STORIES 2018 8

Hematologic Malignancies: Haploidentical Stem Cell Transplant By Isabel Cunningham MD

I n hematologic malignancies, I am choos- ing the wide acceptance of haploidentical stem cell transplant for acute leukemia as the top story of 2018. This is illustrated by two very large cooperative studies published at the end of this year that show haploidentical

transplants achieving similar results to unrelated donor transplants. The European Bone Marrow Transplant Group reported results of 199 haploidentical donor compared to 1494 unrelated donor transplants in adults with relapsed/refractory AML, 1 and an Italian study of children with AML and ALL in remission compared 98 alpha/beta T and B cell–depleted transplants to 245 from unre- lated donors. 2 Comparable CR rates over 77% and 2-year DFS of 23% to 28% were obtained in the 218-center EBMT report. In the pediatric report of patients transplanted in remission, 5-year DFS was 55% to 67% in the compared arms. It is a true advance for our field that we have finally arrived at acceptance of haploidentical donors that enlarges the availability of transplant to virtually every eligible patient, and decreases the cost and prolonged time often required to find a suitable unrelated donor. Delays increase the risk of relapse and transplant failure. It should not have taken 20 years after the NEJM publication of the success of T cell–depleted haploidentical transplant in adult leu- kemia by Aversa et al. 3 That work was the logical extension of the T-cell technique pioneered in the 1980s by Yair Reisner and the Memorial Sloan Kettering group, which enabled parental marrow transplant to children with severe combined immune deficiency. The advent of techniques to harvest “mega-doses” of peripheral

stem cells in the 1990s made it possible to overcome rejection of haploidentical grafts while decreasing the risk of GvHD by T-cell depleting the grafts. Ongoing improvements in conditioning reg- imens and GvHD prevention increase the age of patients whose leukemia may be cured after transplant. Together with continuing development of CAR T-cell therapies, immunologic approaches are major advances in leukemia in 2018. References 1. Brissot E, Labopin M, Ehninger G, et al. Haploidentical versus unrelated allogeneic stem cell transplantation for relapsed/refractory acutemyeloid leukemia: A report of 1578 patients from the Acute Leukemia Working Party of EBMT. Haematologica 2018 Oct 25. doi: 10.3324/haematol.2017.187450. [Epub ahead of print.] 2. Bertaina A, Zecca M, Buldini B, et al. Unrelated donor vs HLA-haploidentical alpha/beta T-cell and B-cell depleted HSCT in children with acute leukemia. Blood 2018 Oct 22. doi: 10.1182/blood-2018-07-861575. [Epub ahead of print.] 3. Aversa F, Tabilio A, Velardi A, et al. Treatment of High-Risk Acute Leukemia

with T-Cell–Depleted Stem Cells from Related Donors with One Fully Mismatched HLA Haplotype. N Engl J Med 1998; 339(17):1186-1193. www.practiceupdate.com/c/76013 ER-Positive, Node-Negative Breast Cancer By Jeffrey J. Kirshner MD, FACP T he ASCO presentation and simulta- neous publication of the results of the TAILORx trial have led to a major change therapy for the primary endpoint of invasive disease-free survival (83.3% vs 84.3%). Noninferiority was also demonstrated in a num- ber of secondary endpoints, including overall survival (93.9% vs 93.8% in the chemoendocrine group). However, in an exploratory analysis of women 50 years of age and younger, there was some benefit of chemotherapy, which needs to be discussed with these patients, particularly with those who have RS 20 to 25. in the adjuvant management of women with ER-positive, node-negative breast cancer. 1 The standard of care has been to treat such

The take-home message is that it is “safe” to omit adjuvant chemo- therapy for most women with ER-positive, node-negative breast cancer with intermediate RS, which is a major practice change affecting thousands of women in the US annually and many more worldwide. Reference: 1. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 2018;379(2):111-121 www.practiceupdate.com/c/74293

patients who have low recurrence scores (RS) on the Oncotype DX assay with hormonal therapy alone and to add chemotherapy for patients with high RS. However, the majority of these patients have RS in the intermediate range, and it has been unknown how much chemotherapy adds to endocrine therapy in this setting. In this trial, 6711 women with intermediate RS (11–25) were ran- domized to endocrine therapy alone versus the addition of chemotherapy prior to starting the hormonal treatment. At 9 years, endocrine therapy alone was noninferior to chemoendocrine

PRACTICEUPDATE ONCOLOGY