Novel Therapies for Blood Diseases

New research on the genetics of different cancers has propelled the advance of new, novel treatment methods for diseases such as leukemia, lymphoma, and myeloma. The 57th ASH Annual Meeting and Exposition was a major platform for some of the most recent data on developing therapies rapidly approaching the market. 

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Acute myeloid leukemia (AML) is one of the most common forms of adult leukemia. Advances in the genetic understandings of AML have found that about 30% of all patients who have a mutation in the FLT3 gene present with a particularly poor prognosis. The cancer in these patients tends to be more aggressive and associated with a much higher incidence of relapse. In his presentation, Richard M Stone, MD (Dana-Farber Cancer Institute, Boston, MA), discussed the value of adding midostaurin, an experimental drug that inhibits the mutated FLT3 enzyme, to standard chemotherapy for improving survival in AML patients. The study included 717 adult AML patients with the FLT3 mutation, 360 of whom received midostaurin and 357 who received a placebo, both in addition to chemotherapy. Dr Stone reported that patients receiving midostaurin failed to achieve remission, relapse, or death for 8 months, compared with just 3 months in the standard treatment arm. In addition, treatment with chemotherapy and midostaurin plus 1 year of maintenance therapy improved median overall survival (74.7 months) versus standard therapy (26 months). Though early, the findings are promising for this patient population. 

A second presentation by Sébastien Maury, MD (Hôpital Henri Mondor, Créteil, France), reported the outcomes of treatment with rituximab, a drug engineered to target CD20, an antigen found on the surface of B cells in 30–50% of patients with B-cell precursor acute lymphocytic leukemia (BCP-ALL). Investigators randomized 202 patients to receive chemotherapy with or without rituximab. Dr Maury stated that, after a median follow-up of 30 months, rituximab was very well tolerated and was associated with a significantly lower incidence of relapse compared with chemotherapy alone (18% vs 30.5%). Two-year event-free survival was also significantly improved in the rituximab arm (65% vs 52%). Dr Maury concluded that adding rituximab to standard therapy could improve outcomes for BCP-ALL patients. 

Alessandra Tedeschi, MD (Azienda Ospedaliera Niguarda Cà Granda, Milano Italy), also reported promising results in her presentation on the targeted therapy ibrutinib for chronic and small lymphocytic leukemia (CLL/SLL). For older adults, chlorambucil is the current standard first-line therapy. In a phase 3 study comparing ibrutinib with chlorambucil for up to 12 treatment cycles in 269 patients with CLL/SLL and a median age of 73 years, patients treated with ibrutinib achieved better 18-month progression-free survival rates than those treated with chlorambucil (93.9% vs 44.8%). Twenty-four-month overall survival rates were also significantly improved (97.8% vs 85.3%). Citing these results, Dr Tedeschi suggested the inclusion of ibrutinib in this patient population. 

Andrew D Zelenetz, MD, PhD (Memorial Sloan Kettering Cancer Center, New York, NY), also presented a study evaluating rituximab, this time in comparison with another drug, idelalisib. Idelalisib is already approved in combination with rituximab for the treatment of CLL, but researchers tested whether adding it to rituximab plus bendamustine (BR)—the current standard for patients with relapsed CLL—could further improve outcomes. In the trial, 207 patients received idelalisib with BR, while 209 patients received a placebo plus BR. Treatment continued until disease progression or if toxicity effects became unbearable. 

The primary endpoint of progression-free survival was significantly improved in the idelalisib arm compared with the placebo arm (23 vs 11 months). In addition, overall survival was significantly improved among those treated with idelalisib and BR as opposed to BR and placebo. The safety of both groups was comparable, with major adverse events including low white blood cell count and anemia. It was concluded that idelalisib plus BR provides better outcomes than BR alone for patients with relapsed CLL, and with tolerable side effects. Dr Zelenetz stated that the study results were originally not intended to be released, but the overwhelming efficacy of the drug led to the recommendation that the results be unblinded.

The presentations at the ASH Annual Meeting shed an optimistic light on some of the research being conducted to improve treatment for blood disorders and also represent what seems to be the growing focus of cancer care: more personalized, genetically targeted therapies.