Angioimmunoblastic T-cell lymphoma (AITL) is a frequent subtype of peripheral T-cell lymphoma (PTCL) that is clinically characterized by generalized lymphadenopathy, extranodal involvement, advanced ...stage at presentation, hypergammaglobulinemia, and significant immune dysregulation resulting in infections as the most common cause of death. Recent advances in pathobiology of AITL have improved our understanding of it as a clonal T-cell disorder and of its effect on B cells in the tumor microenvironment. Reponses to first-line therapies have largely been dismal. In this review, we discuss the clinical features, pathobiology, prognostic models, standard therapy, and newer therapeutic agents used and their implications for the future.
We used the Therapy Preference Scale, a 30-item questionnaire, to determine cancer treatment preferences of adults with cancer.
We used Wilcoxon's rank sum test and Fisher's exact test to compare the ...preferences of younger (<60 years) versus older adults (≥60 years).
While 56% of patients would accept treatment offering increased life expectancy at an expense of short-term side effects, 75% preferred maintenance of cognition, functional ability and quality of life to quantity of days. Oral instead of intravenous treatment (p = 0.003), shorter hospital stay (p = 0.03), preservation of cognitive function (p = 0.01) and avoidance of pain (p = 0.02) were more important to older patients compared with younger patients.
Many patients prioritized maintenance of cognition, functional ability and quality of life; older patients valued oral treatment, shorter hospital stay, preservation of cognitive function and avoidance of pain.
Summary
Improved maintenance treatments are needed for patients with relapsed/refractory aggressive lymphomas after autologous haematopoietic stem cell transplantation (ASCT). Several studies with ...lenalidomide have been found to have activity in the treatment of relapsed/refractory aggressive lymphomas. In the present phase I/II, single‐arm, open‐label study, 59 patients with high‐risk relapsed non‐Hodgkin lymphoma received pretransplant BEAM chemotherapy and ASCT followed by 12 months of maintenance lenalidomide once daily on Days 1–21 (28‐day cycles) beginning at post‐transplantation Day 100. The most common histologies were mantle cell lymphoma (56%) and diffuse large B‐cell lymphoma (24%). The maximum tolerated dose in the dose‐finding part of the study was 15 mg, but cytopenias led to the subsequent adoption of a 10 mg dose in the final study. Sixteen patients (27%) completed 12 cycles of lenalidomide maintenance. The most common reason for discontinuation was adverse events (31%). These were primarily haematologic, and 56% of patients experienced Grade 3–4 events. Two‐year PFS rates (95% CIs) were 70% (56%–80%), 45% (19%–68%) and 81% (66%–90%); 2‐year OS rates (95% CIs) were 91% (80%–96%), 93% (61%–99%) and 90% (76%–96%) in all patients, patients completing and patients not completing 12‐month maintenance respectively. These results do not support the use of lenalidomide maintenance in this setting.
High-grade B-cell lymphomas with MYC, BCL2, and/or BCL6 rearrangements, “double-hit” or “triple-hit” lymphomas (DTHL), are aggressive neoplasms associated with a poor prognosis. A t(3;8)(q27;q24) ...rarely occurs in B-cell lymphomas that results in a unique “pseudo–double-hit” BCL6-MYC fusion, indistinguishable by interphase fluorescence in situ hybridization (FISH) from more conventional DTHL with independent MYC and BCL6 translocations. Reports of t(3;8)(q27;q24) lymphomas are sparse, and to better characterize their pathologic, cytogenetic, and clinical features, 6 new cases from 2 institutions and 19 previously published cases were reviewed. All new cases displayed aggressive morphologic features, and most previously published cases were classified as aggressive lymphomas. Collectively, all t(3;8)(q27;q24) cases had a germinal center (GC) phenotype, and most had complex karyotypes (22/24, 92%), including frequent concomitant BCL2 rearrangements (17/24, 71%). When compared to two large published DTHL cohorts, t(3;8)(q27;q24) lymphomas less often expressed BCL2 (P < .01), had a greater likelihood of extranodal involvement (P < .01), and more frequently appeared triple-hit by FISH analysis (P < .01). Despite presenting with aggressive clinicopathologic features, 100% (6/6) of t(3;8;)(q27;q24) patients achieved complete remission after intensive induction regimens, and 2- and 3-year overall survival rates were 63% (10/16) and 57% (8/14), respectively. These findings suggest that lymphomas with t(3;8)(q27;q24) may represent a subset of GC B-cell lymphomas distinct from conventional DTHL. Our results further highlight the value of routine karyotype assessment in aggressive B-cell lymphomas, and the importance of recognizing the t(3;8)(q27;q24) so that its clinical significance can be more fully explored.
•Reciprocal BCL6-MYC translocation occurs in a subset of aggressive B-cell lymphomas.•Lymphomas with BCL6-MYC are not easily distinguished from true double-hit lymphomas.•These lymphomas have a germinal center origin and frequent BCL2 translocations.•Lymphomas with BCL6-MYC may have better outcomes than true double-hit lymphomas.
Phase 1 testing of SGN-30, a chimeric monoclonal antibody for the treatment of CD30+ malignancies, was conducted in a multicenter study. To explore the safety profile and establish the maximum ...tolerated dose (MTD), 24 patients with refractory or relapsed Hodgkin lymphoma or CD30+ non-Hodgkin lymphoma received 6 weekly doses of intravenous SGN-30 at 4 dose levels (2, 4, 8, or 12 mg/kg). Serum concentrations of SGN-30 rose rapidly and were dose dependent. Adverse events were mild, with nausea, fatigue, and fever attributed to study treatment. One episode of hypersensitivity rash was reported. The MTD was not reached. Serious adverse events included herpes zoster (n = 2), influenza, and pneumonia. One patient with cutaneous anaplastic large cell lymphoma (8 mg/kg) achieved a complete response. Six patients, of whom 4 had Hodgkin lymphoma, achieved stable disease with durations ranging from 6 to 16 months. The pharmacokinetic profile of SGN-30 showed a biphasic disposition, and estimated half-lives ranging between 1 to 3 weeks. The 6 weekly infusions of SGN-30 resulted in approximately 2- to 3-fold accumulation in serum exposures consistently across the dose range. These results demonstrate that weekly administration of SGN-30 is safe and has modest clinical activity in patients with CD30+ tumors. This trial is registered at http://www.ClinicalTrials.gov as no. NCT00051597.
Follicular lymphoma (FL) is a common low-grade lymphoma with excellent long-term survival in the present era. We used the Surveillance, Epidemiology, and End Results registry to identify patients ...with FL from 1992 to 2010 and study the incidence and risk factors for the development of second primary malignancies (SPMs). During a median follow-up period of 71 months, 1540 patients (9.9%) developed SPMs, with a cumulative incidence of 11% at 10 years and an increased risk of both hematologic and solid malignancies. This risk was significantly increased among patients aged > 65 years, males, and those receiving radiation therapy.
With the improving outcomes of patients with follicular lymphoma (FL), it is imperative to focus on survivorship issues, including the development of second primary malignancies (SPMs). We used a large US database to measure the risk of SPMs among FL survivors.
We used the Surveillance, Epidemiology, and End Results-13 registry to identify FL patients from 1992 to 2011. We calculated the risk of SPMs, developing ≥ 6 months after diagnosis, using the standardized incidence ratio (SIR) and absolute excess risk. We calculated the cumulative incidence of SPMs using the competing risk method and risk factors for SPMs using univariate and multivariate methods.
Of a total of 15,517 patients with FL followed up for a median of 71 months, 1540 (9.9%) developed SPMs, with a SIR of 1.08 and absolute excess risk of 11.3 per 10,000 person-years. A significantly increased risk was noted for Hodgkin lymphoma (SIR, 5.85), acute myeloid leukemia (SIR, 4.88), and the following sites: oral cavity and pharynx (SIR, 1.43), stomach (SIR, 1.43), lung and bronchus (SIR, 1.35), melanoma of skin (SIR, 1.38), other nonepithelial cancers of the skin (SIR, 2.88), urinary bladder (SIR, 1.24), and kidney/renal pelvis (SIR, 1.43). The cumulative incidence of SPMs was 11.06% at 10 years. Multivariate regression showed that age > 65 years (SIR, 1.57; P < .001), male gender (SIR, 1.43; P < .001), and receipt of radiation (SIR, 1.24; P = .001) predicted a higher rate of SPMs.
Patients with FL have increased risk of both hematologic and solid malignancies. Risk factors for SPMs include advanced age, male gender, and receipt of radiation therapy.
Brentuximab vedotin has emerged as a useful treatment option for relapsed or refractory Hodgkin's lymphoma; however, uncommon cases of anaphylactic reactions may require its permanent ...discontinuation. We report a 29‐yr‐old woman with refractory Hodgkin's lymphoma, who developed an anaphylactic reaction during the second dose of brentuximab vedotin. A 12‐step desensitization protocol was followed; after premedicating with antihistaminic agents, methylprednisolone and montelukast, a total dose of 156 mg of brentuximab vedotin (1.8 mg/kg) was given as three infusions with increasing rate and concentration. Such desensitization protocol can allow safe administration of brentuximab vedotin and may have a broader applicability in managing hypersensitivity reactions with other monoclonal antibodies.
Morphologic heterogeneity is only part of the picture for patients with high‐grade B‐cell lymphomas, and many of these lymphomas are biologically driven by equally complex variations in genetics and ...protein expression. In this patient population, novel targeted therapies need to be tested in combination with chemoimmunotherapy in the front‐line setting, because the proportion of patients who progress early is so high, and many patients do not appear to be salvageable with further conventional chemotherapy regimens.
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