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Abstract Background: Treatment of Hodgkin lymphoma (HL) requires a careful balance between providing enough therapy to cure the disease and avoiding unnecessary treatment that could result in excessive long-term treatment-related complications. The preferred treatment option for limited stage non-bulky HL currently involves the use of combined chemotherapy and involved-field radiation therapy. Given the unclear overall survival advantage and the long-term side effects associated with consolidative radiation, the use of this modality remains one of the most controversial topics in the treatment of HL. Therefore, alternative consolidation approaches are worthy of exploration for treatment of limited stage non-bulky HL. Brentuximab vedotin has been associated with favorable response rates in patients with relapsed or refractory HL. We hypothesize that brentuximab vedotin may be safe and effective in eradicating residual disease after induction chemotherapy and may potentially replace radiation therapy for consolidation in patients with newly diagnosed limited stage non-bulky HL. Methods: In this phase 2 multicenter study, patients with non-bulky (< 7.5 cm) stage I or II HL are being enrolled to determine the efficacy and safety of brentuximab vedotin when administered for consolidation after a standard chemotherapy with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) (ClinicalTrials.gov #NCT01578967). The primary objective of the study is to estimate the proportion of patients who achieve PET-negative disease (Deauville score of 2 or less) after induction chemotherapy followed by consolidation with brentuximab vedotin. Involved-field radiation is recommended only if the PET scan is positive at the completion of therapy with brentuximab vedotin. Patients received 2 to 6 cycles of ABVD based on their baseline risk factors and the interim PET scan result; patients with favorable disease with negative interim PET received 2 cycles, favorable disease with positive interim PET or unfavorable disease with negative interim PET received 4 cycles, and unfavorable disease with positive interim PET received 6 cycles of ABVD. Approximately 6 to 8 weeks after the induction chemotherapy, 1.8 mg/kg of brentuximab vedotin was given every 3 weeks for 6 cycles for consolidation. Results: Interim analysis was performed per protocol for futility and safety after 15 evaluable patients were enrolled since April 2012. Out of 15 evaluable patients, 8 patients have completed 6 cycles of brentuximab vedotin, and the remaining 7 patients are currently under active treatment. The median age was 28 years (range 19 – 58), and 7 patients (47%) presented with unfavorable disease defined by the presence of B symptoms, ESR > 50, or > 3 sites of disease. All patients had masses measuring less than 7.5 cm in diameter except one patient who requested an exception to the eligibility criteria for a conglomerate mediastinal mass measuring 10 cm. No grade 3 or above adverse events have been observed with brentuximab vedotin therapy. No grade 2 or above peripheral neuropathy or pulmonary toxicity has been reported. Ten out of 12 patients, who completed ABVD, achieved PET-negative disease after 2 cycles of ABVD, and all 7 patients who completed brentuximab vedotin achieved PET-negative disease and remain in remission with a median follow-up of 7.6 months (range 5.6 – 15). Thus far, none of the treated patients on this protocol required consolidative radiation therapy. Conclusion: In this interim analysis of 15 patients with newly diagnosed limited stage non-bulky HL, brentuximab vedotin as consolidation therapy demonstrates promising safety and clinical activity following ABVD. Enrollment is currently open with the target accrual of 40 patients to assess the feasibility of achieving PET-negative disease and thereby avoiding radiation therapy in at least 85% of patients who receive ABVD followed by brentuximab vedotin consolidation. Table: PET results in HL patients who received ABVD followed by BV Consolidation Interim-PET2 (n = 12) Post ABVD (n = 12) Post BV (n = 7) Deauville 1 0 1 4 Deauville 2 10 11 3 Deauville 3 2 0 0 Deauville ≥ 4 0 0 0 PET, positron emission tomography; HL, Hodgkin lymphoma; ABVD, doxorubicin, bleomycin, vinblastine, dacarbazine; BV, brentuximab vedotin; Interim-PET-2, PET scan after 2 cycles of ABVD; Post ABVD, PET scan after 2 to 6 cycles of ABVD; Post BV, PET scan after 6 cycles of brentuximab vedotin Disclosures Park: Seattle Genetics: Research Funding; Teva: Research Funding; Janssen: Travel, Travel Other. Off Label Use: Brentuximab vedotin in previously untreated Hodgkin lymphoma patients.

SummaryAggressive induction chemotherapy followed by autologous haematopoietic stem cell transplant (auto‐HCT) is effective for younger patients with mantle cell lymphoma (MCL). However, the optimal induction regimen is widely debated. The Southwestern Oncology Group S1106 trial was designed to assess rituximab plus hyperCVAD/MTX/ARAC (hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone, alternating with high dose cytarabine and methotrexate) (RH) versus rituximab plus bendamustine (RB) in a randomized phase II trial to select a pre‐transplant induction regimen for future development. Patients had previously untreated stage III, IV, or bulky stage II MCL and received either 4 cycles of RH or 6 cycles of RB, followed by auto‐HCT. Fifty‐three of a planned 160 patients were accrued; an unacceptably high mobilization failure rate (29%) on the RH arm prompted premature study closure. The estimated 2‐year progression‐free survival (PFS) was 81% vs. 82% and overall survival (OS) was 87% vs. 88% for RB and RH, respectively. RH is not an ideal platform for future multi‐centre transplant trials in MCL. RB achieved a 2‐year PFS of 81% and a 78% MRD negative rate. Premature closure of the study limited the sample size and the precision of PFS estimates and MRD rates. However, RB can achieve a deep remission and could be a platform for future trials in MCL.

BACKGROUNDPatients with FMS like tyrosine kinase 3 (FLT3)‐mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT).METHODSData from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes.RESULTSIn total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild‐type (WT) group (38% [95% confidence interval (CI), 30%‐45%] vs 28% [95% CI, 24%‐33%]; P = .04; relative risk, 1.60 [95% CI, 1.15‐2.22]; P = .0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia‐free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3‐year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%‐57%; WT group: 55%, 95% CI, 50%‐60%; P = .20).CONCLUSIONSThe current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long‐term survivors. Cancer 2016;122:3005‐3014. © 2016 American Cancer Society.

Key PointsHCT recipients have increased susceptibility to herpes zoster, but live-attenuated vaccines are not appropriate for highly immunocompromised people. An adjuvanted subunit vaccine against herpes zoster elicits strong immune responses with an acceptable safety profile in adult autologous HCT recipients.

BACKGROUND Recombinant interleukin‐2 (rIL‐2) induces cellular cytotoxicity against leukemia blasts. Patients with acute myeloid leukemia (AML) in first complete remission (CR) may harbor minimal residual disease that is susceptible to rIL‐2–activated effector cells. METHODS In the Cancer and Leukemia Group B (CALGB) 19808 study, patients with AML in first CR were randomly assigned after all planned chemotherapy to receive a 90‐day course of subcutaneously administered rIL‐2 or no further therapy. The primary objective was to compare disease‐free survival (DFS) between the 2 treatment arms. A total of 534 patients achieved a CR, 214 of whom were randomized. Six courses of low‐dose daily rIL‐2 were given for the expansion of cytotoxic effector cells, each followed by 3‐day high‐dose boluses given to trigger cytotoxicity against minimal residual disease. RESULTS On the protocol‐specified intention‐to‐treat analysis, the hazards ratio for DFS was 0.75 (95% confidence interval, 0.52‐1.09; P = .13); the 5‐year DFS rate was 42% in the observation arm and 53% in the rIL‐2 treatment arm. The hazards ratio for overall survival (OS) was 0.88 (95% confidence interval, 0.54‐1.23; P = .34); the 5‐year OS rate was 58% for the observation arm and 63% for the rIL‐2 treatment arm. Twenty‐five of the 107 patients randomized to treatment with rIL‐2 either refused or were unable to initiate therapy and 30 patients did not complete their assigned therapy. However, significant toxicities were not commonly observed. The trial design did not anticipate the difficulties patients would encounter with protocol compliance. CONCLUSIONS The efficacy of immunotherapy with rIL‐2 administered after intensive postremission treatment was not assessed as planned because of unexpected refusals by patients and/or their physicians to comply with protocol‐directed therapy. Neither DFS nor OS was found to be significantly improved. Cancer 2014;120:1010–1017 . © 2013 American Cancer Society .