Clinical Outcomes of Patients with Anaplastic Large Cell Lymphoma, Anaplastic Lymphoma Kinase-Positive (ALCL, ALK+): Data from 119 Patients Prospectively Registered in the International T-Cell Project

Introduction: Anaplastic Large Cell Lymphoma, Anaplastic Lymphoma Kinase-positive (ALCL, ALK+) is a clinically aggressive lymphoid neoplasm with reported outcomes that compare favorably to other peripheral T-cell lymphoma (PTCL) subtypes. Pathogenesis of ALCL, ALK+ has been linked to perpetual activation of the ALK-kinase and numerous downstream signaling molecular events, that result from the recurrent genetic alteration, t(2;5)(p23;q35), in the majority of cases. In this study, we sought to analyze demographic characteristics, presenting clinical features, and treatment outcomes of 116 patients with ALK+ ALCL prospectively enrolled into the international T-cell lymphoma registry, the T-cell Project (TCP).

Methods: The T-Cell Project prospectively registered consecutive patients with newly diagnosed PTCLs from 74 centers, in 14 countries, across 4 continents from Sep 2006 -Dec 2015. A key aim of this global collaborative project was to more precisely define clinical characteristics and outcomes of patients with various PTCL subtypes.

Results: From a total of 1,429 evaluable PTCL cases, 119 (8.3%) were confirmed as ALCL, ALK+ following international histopathologic panel review. As anticipated, these cases, as a proportion of all PTCL cases, varied across geographical regions (Asia 4.4%, South America 8.0%, U.S.A 9.3%, and Europe 9.1%). The median age at diagnosis was 34.5 (range, 18-84) years with a slight male predominance (58%). Stage III/IV disease was found in 68.7% patients, whilst bulky disease >10cm (8.4%) and bone marrow involvement (14.5%) were uncommon, and 78.6% of patients had low risk IPI score (0-1). Data on therapy was available in 81 (68%) patients, of whom 80 (99%) received chemotherapy (CHT) as part of first-line treatment. Ten patients (12.3%) additionally received concurrent or sequential radiotherapy (RT), whilst 4 patients (4.9%) underwent high-dose therapy as consolidation. One patient (1.2%) received palliative care only. Of 80 patients treated with chemotherapy, 76 (91%) received anthracycline-containing regimens. The investigator-assessed overall response rate was 82.6%, with 57 patients (71%) achieving complete remission. With a median follow-up of 28 (range, 19-37) months, the median PFS for (n=114) ALK+ ALCL patients was not reached, and 3-year and 5-year PFS rates were 66% (95% CI, 55-75) and 59% (95% CI, 47-70), respectively. The median OS (n=116) was not reached, and 3-year and 5-year OS rates were both 77% (95% CI, 66-85) (Fig.1). At the time of data cut off, 20 patients died. Cause of death was most commonly attributable to lymphoma (65%) and infection (15%).

Conclusions: This is the largest prospective international registry study to-date of ALCL, ALK+ patients, describing epidemiology, clinical features, treatment approaches and clinical outcomes. The use of anthracycline-based CHT regimens remains a standard of care front-line approach across global geographic regions. With a median follow up of >2 years, we observed favorable OS outcomes compared to other PTCLs despite presence of advanced stage disease in the majority of patients. However, the rates of PFS leave room for improvement. These findings are consistent with previous report from the retrospective International T-cell Project. Incorporation of recently developed CD30-targeting and ALK-kinase targeting agents into front-line regimens is underway to further improve outcomes for high-risk patients.

Figure 1. Kaplan-Meier estimates of overall (A) and progression-free survival (B) among ALCL, ALK+ patients enrolled into the prospective TCP registry.

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