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CML Patients Still Benefit from Transplant

— Also at SOHO: Ponatinib proves mettle in pretreated CML

Last Updated September 16, 2016
Ƶ MedicalToday

HOUSTON -- Even in the era of effective systemic therapies, stem cell transplant has retained a key role in the management of chronic myeloid leukemia (CML), a retrospective review suggested.

Over the 12-year period ending in 2013, the 67 patients underwent stem-cell transplants following at least one line of treatment with a tyrosine kinase inhibitor (TKI). The review of patient records showed that the primary circumstance leading to transplant was development of advanced disease (36% of cases), , of Moffitt Cancer Center in Tampa, Fla., and colleagues reported at the Society of Hematologic Oncology meeting. The next most common reason was TKI resistance (30%).

Action Points

  • Note that this studies were published as abstracts and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

The patients had a median age of 44 and had received as many as four prior TKIs, which produced a best response of major molecular response in 27% of patients, major cytogenetic response in 30%, and complete hematologic response in 15%.

Posttransplantation patients had a 5-year overall survival (OS) of 47% and disease-free survival (DFS) probability of 40% at 5 years. The 5-year probability of nonrelapse mortality was 33%.

The number of prior TKIs, presence of T3151 mutation, and receipt of posttransplant TKIs did not affect long-term outcomes. Transplantation in chronic phase CML or patients with low Armand risk scores was associated with improved OS and DFS.

Long-Term Survival with BCR-ABL Inhibitor

Three-fourths of patients with heavily pretreated CML remained alive at 4 years following treatment with the oral BCR-ABL inhibitor ponatinib (Iclusig), results from a single-arm phase II trial showed.

The 270-patient cohort had an estimated 4-year survival of 77% and estimated progression-free survival (PFS) of 56%, , of the MD Anderson Cancer Center in Houston, and colleagues reported. The most common adverse events were rash (47%), abdominal pain (46%), thrombocytopenia (45%), headache (43%), constipation (41%), and dry skin (41%). The cumulative incidence of arterial occlusive disease was 29%, although the risk declined over time.

For the entire cohort, 59% of patients achieved a major cytogenetic response at some point during treatment and follow-up, and 54% attained a complete cytogenetic response. Additionally, 39% of patients achieved a major molecular response, 29% a 4-log molecular response, and 23% a 4.5-log molecular response. A similar proportion of patients with resistant disease or intolerance (n=203) attained the various degrees of response, and patients with T3151 mutations (n=64) did as well or better than the overall cohort.

Responses tended to be durable despite frequent dose reductions, the investigators reported. Among patients who attained major cytogenetic or molecular response, more than 90% maintained the response 22 months after dose reduction.

Outcomes Still Dismal for Many with DLBCL

About a fourth of 635 patients with refractory, aggressive diffuse large B-cell lymphoma (DLBCL) achieved objective responses to currently available therapies, according to a meta-analysis of outcomes in chemorefractory disease.

The overall response rate was 26% and ranged from 21% to 31% across the four patient populations included in the analysis. Median OS was 6 to 7 months and did not vary substantially by patient group.

"This consistently poor outcome represents a significant unmet medical need," , of Queen's University in Kingston, Ontario, reported on behalf of colleagues representing two phase III studies and two observational cohort studies.

The analysis included patients who had progressive disease or stable disease <12 weeks as best response to most recent chemotherapy or relapse within 12 months of autologous stem-cell transplant. These and other high-risk or poor-prognosis patients with lymphoma and leukemia have been the focus of CAR T-cell therapy as the treatment has evolved over the past several years.

  • author['full_name']

    Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined Ƶ in 2007.

Disclosures

Sweet and Crump disclosed no relevant relationships with industry.

Cortes disclosed relevant relationships with Ariad, Bristol-Myers Squibb, Novartis, Pfizer, and Teva.

Several co-authors disclosed multiple relevant relationships with industry, including companies that develop and market therapies used to treat hematologic malignancies.

Primary Source

Society of Hematologic Oncology

Sweet K, et al "Indications and outcomes of allogeneic stem cell transplant for chronic myeloid leukemia in the era of tyrosine kinase inhibitors" SOHO 2016; Abstract CML-193.

Secondary Source

Society of Hematologic Oncology

Cortes J, et al "Four-year results from the pivotal phase II PACE trial: Efficacy and safety in heavily pretreated leukemia patients" SOHO 2016; Abstract CML-048.

Additional Source

Society of Hematologic Oncology

Crump M, et al "Outcomes in refractory aggressive diffuse large B-cell lymphoma (DLBCL): Results from the international SCHOLAR-1 study" SOHO 2016; Abstract NHL-088.