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Alemtuzumab shows promise for T-cell large granular lymphocytic leukemia
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A single treatment course of alemtuzumab appeared to produce a hematological response in patients with relapsed and refractory T-cell large granular lymphocytic leukemia, according to interim results from a phase 2 study.
These results suggest that hematological response can be achieved without the continued use of an oral immunosuppressive agent, according to the researchers.
Tapan M. Kadia
Patients with T-cell large granular lymphocytic leukemia (T-LGL) often present with immune-mediated cytopenias, which can be treated with first-line therapy consisting of methotrexate, ciclosporin or cyclophosphamide. However, long-term use of these agents can lead to toxicity, according to study background.
Thus, Phillip Scheinberg, MD, staff clinician in the hematology branch at the NHLBI, and colleagues sought to determine the safety and efficacy of the anti-CD52 monoclonal antibody alemtuzumab (Lemtrada, Genzyme) in patients with T-LGL.
Scheinberg and colleagues conducted a single-arm, open-label phase 2 study in which they assigned patients to 10 mg IV alemtuzumab daily for 10 days.
Hematological response at 3 months after infusion served as the primary endpoint. Researchers defined a complete hematologic response as normalization of all affected lineages. They defined a partial hematologic response in neutropenic patients as a 100% increase in the absolute neutrophil count to more than 5 x 108 cells per L, and in patients with anemia as any increase in hemoglobin of 20 g/L or higher in two serial measurements at least 1 week apart that were sustained for at least 1 month without exogenous growth factors support or transfusions.
The researchers reported interim results of the trial, which included data from 25 patients (median age, 61 years; 56% women; median prior therapies, n = 3).
Median follow-up was 31.1 months (interquartile range, 6.6-61.1).
Fourteen patients achieved a hematological response at 3 months (56%; 95% CI, 35-76). Because four patients with associated myelodysplastic syndrome and two patients who had undergone hematopoietic stem cell transplantation achieved no response or remained unevaluable, the researchers determined that 74% (95% CI, 49-91) of patients with classic T-LGL responded to treatment.
All patients experienced infusion reactions, 96% (n = 24) of which were grade 1 or grade 2. All infusion reactions improved with symptomatic therapy.
Further, all patients developed lymphopenia, with 88% (n = 22) developing grade 3 or grade 4 lymphopenia. Other frequently observed grade 3 to grade 4 adverse events included leukopenia (32%; n = 8) and neutropenia infections (20%; n = 5).
Seven patients — all nonresponders to treatment — died.
Farhad Ravandi
The researchers identified limitations of their study, including the single-arm design and the relatively small cohort. However, they asserted that the rarity of the disease prevents the conduct of large randomized controlled trials.
“The continuing enrollment of additional patients with longer follow-up will allow for more precise hematological response rates and assessment of secondary endpoints,” Scheinberg and colleagues wrote.
In an accompanying editorial, Tapan M. Kadia, MD, and Farhad Ravandi, MD, both of the department of leukemia at The University of Texas MD Anderson Cancer Center, noted that the benefits of alemtuzumab must be weighed against potential risks.
“The overall response rate of greater than 50% in a mostly relapsed and refractory population after one course of 10-day therapy is encouraging, but the enthusiasm must be tempered by the potential for profound, prolonged immunosuppression, viral reactivation and other toxicity, particularly in a relatively indolent disorder,” Kadia and Ravandi wrote. “Although the single course of therapy could obviate the need for the chronic intake of immunosuppression, it is substituted, in effect, by chronic prophylactic treatment for opportunistic infections. Patients with T-LGL considered for alemtuzumab should, therefore, be carefully selected, taking into account risk, benefit, activity of other available drugs and targeted clinical trials.” – by Cameron Kelsall
Disclosure: The NHLBI funded this study. The researchers report no relevant financial disclosures. Kadia and Ravandi report grant support from the NIH.
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