Favorable outcomes from allogeneic and autologous stem cell transplantation for patients with transformed nonfollicular indolent lymphoma.

The role of allogeneic (allo-) and autologous stem cell transplantation (auto-SCT) in the management of patients with transformed indolent nonfollicular non-Hodgkin lymphoma is unknown. This is a multicenter, retrospective cohort study of patients with biopsy-proven indolent B cell nonfollicular non-Hodgkin lymphoma and simultaneous or subsequent biopsy-proven aggressive histology transformation who were treated with allo-SCT or auto-SCT between 1996 and 2013. All patients received myeloablative conditioning regimens. Outcomes were compared with a cohort of 246 patients with transformed follicular lymphoma who also underwent allo-SCT (n = 47) or auto-SCT (n = 199) across the same institutions and time frame. Thirty-four patients were identified with the following underlying indolent histologies: 15 (44%) marginal zone lymphoma, 11 (32%) chronic lymphocytic leukemia, 6 (18%) small lymphocytic lymphoma, and 2 (6%) lymphoplasmacytic lymphoma. Patients received various anthracycline or platinum-containing chemotherapy regimens for transformation, incorporating rituximab in 25 (74%). Twelve (35%) subsequently underwent allo-SCT, whereas 33 (65%) underwent auto-SCT. The 3-year overall survival rate after transplantation was 67% (allo-SCT 54%, auto-SCT 74%), and 3-year progression-free survival rate was 49% (allo-SCT 40%, auto-SCT 54%). The 3-year nonrelapse mortality rate was 14% (allo-SCT 15%, auto-SCT 7%). Transplant-related mortality at 100 days was 17% for allo-SCT and 0% for auto-SCT. Adjusted for type of stem cell transplantation, 3-year overall survival, progression-free survival, and nonrelapse mortality rates were similar to those of patients with transformed follicular lymphoma receiving allo-SCT and auto-SCT (P = .38, P = .69, and P = .54, respectively). Allo-SCT and auto-SCT may be reasonable treatments for selected patients with transformed nonfollicular indolent lymphoma, although medium-term outcomes and toxicity appear to be more favorable with auto-SCT.

Limited clinical benefit for surveillance PET-CT scanning in patients with histologically transformed lymphoma in complete metabolic remission following primary therapy.

The optimum follow-up of patients with transformed indolent lymphoma (TrIL) is not well defined. We sought to determine the utility of surveillance positron emission tomography-computed tomography (PET-CT) in patients with TrIL achieving complete metabolic remission (CMR) after primary therapy. We performed a retrospective analysis of patients with TrIL treated at Peter MacCallum Cancer Centre between 2002 and 2012 who achieved CMR after primary therapy who had ≥1 subsequent surveillance PET-CT. Of 55 patients with TrIL, 37 (67 %) received autologous stem cell transplantation as consolidation following chemoimmunotherapy. After a median follow-up of 34 (range 3-101) months, the actuarial 3-year progression-free (PFS) and overall survival (OS) were 77 % (95 %CI 62-86 %) and 88 % (75-94 %), respectively. Of 180 surveillance PET-CT scans, there were 153 true negatives, 4 false positives, 1 false negative, 7 indeterminate and 15 true positives. Considering indeterminate scans as false positives, the specificity of PET-CT for detecting relapse was 94 %, sensitivity was 83 %, positive predictive value was 63 % and negative predictive value was 98 %. All seven subclinical (PET detected) relapses were of low-grade histology; in contrast, all nine relapses with diffuse large B cell lymphoma (DLBCL) were symptomatic. In our cohort of patients with TrIL achieving CMR, PET-CT detected subclinical low-grade relapses but all DLBCL relapses were accompanied by clinical symptoms. Thus, surveillance imaging of patients with TrIL achieving CMR is of limited clinical benefit. PET-CT should be reserved for evaluation of clinically suspected relapse.

High FDG activity in focal fat necrosis: a pitfall in interpretation of posttreatment PET/CT in patients with non-Hodgkin lymphoma.

PURPOSE: PET/CT has a major role in lymphoma imaging, but glycolytic activity in inflammatory processes can reduce specificity. In this study we evaluated restaging PET/CT findings in patients with non-Hodgkin lymphoma (NHL) and fat necrosis. METHODS: We identified 16 patients from 8,819 restaging FDG PET/CT scans with suspicion of or biopsy-proven fat necrosis on PET/CT. RESULTS: All patients had NHL and demonstrated focal FDG-avid nodular change on CT with density higher than that of fat but lower than that of soft tissue. Histological confirmation was obtained in eight patients, with high GLUT-1 staining between necrotic tissue and organizing fat necrosis evident. Uptake resolved in four patients, and surveillance was continuing in four without relapse. CONCLUSION: Although rare, identification of fat necrosis in patients with a solitary FDG-avid nodule after therapy is important and may lead to the avoidance of unnecessary interventions or treatment. Specific features on CT aid identification, whilst follow-up imaging can be helpful as the metabolic abnormality regresses with time.

Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial.

BACKGROUND: Pomalidomide and dexamethasone is a standard of care for patients with multiple myeloma in whom bortezomib and lenalidomide treatment has failed. KEYNOTE-183 assessed efficacy and safety of pomalidomide and dexamethasone with or without pembrolizumab in patients with relapsed or refractory multiple myeloma. Here, we present the findings of an unplanned, ad-hoc interim analysis at the request of the US Food and Drug Administration (FDA). METHODS: KEYNOTE-183 was a randomised, open-label, phase 3 trial done at 97 medical centres across 11 countries (Australia, Canada, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Spain, and USA). Patients aged at least 18 years with multiple myeloma, an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, previously treated with at least two lines of therapy (excluding pomalidomide) and refractory to the last line were randomly assigned 1:1 to the pembrolizumab plus pomalidomide and dexamethasone group or the pomalidomide and dexamethasone group via an interactive voice response or integrated web response system. Patients received oral pomalidomide 4 mg daily on days 1-21 and oral low-dose dexamethasone 40 mg on days 1, 8, 15, and 22 in 28-day cycles, with or without intravenous pembrolizumab 200 mg every 3 weeks. The dual primary endpoints were progression-free survival and overall survival. Efficacy was assessed in all randomly assigned patients and safety was assessed in patients who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov, number NCT02576977, and it is closed for accrual. FINDINGS: Between Jan 18, 2016, and June 7, 2017, 249 patients were randomly assigned to either the pembrolizumab plus pomalidomide and dexamethasone group (n=125) or the pomalidomide and dexamethasone group (n=124). On July 3, 2017, the FDA established that risks associated with the triple combination outweighed benefits and halted the study. Median follow-up was 8·1 months (IQR 4·5-10·9). Median progression-free survival was 5·6 months (95% CI 3·7-7·5) in the pembrolizumab plus pomalidomide and dexamethasone group versus 8·4 months (5·9-not reached) in the pomalidomide and dexamethasone group; progression-free survival estimates at 6 months were 48% (95% CI 37-58) versus 60% (49-69) at 6 months (hazard ratio [HR] 1·53; 95% CI 1·05-2·22; p=0·98). Median overall survival was not reached (95% CI 12·9-not reached) versus 15·2 months (12·7-not reached; HR 1·61; 95% CI 0·91-2·85; p=0·95); overall survival estimates at 6 months were 82% (95% CI 74-88) versus 90% (82-95). Serious adverse events occurred in 75 (63%) of 120 patients in the pembrolizumab plus pomalidomide and dexamethasone group versus 56 (46%) of 121 patients in the pomalidomide and dexamethasone group. Four (3%) treatment-related deaths occurred in the pembrolizumab plus pomalidomide and dexamethasone group (one each of unknown cause, neutropenic sepsis, myocarditis, and Stevens-Johnson syndrome); myocarditis and Stevens-Johnson syndrome were considered related to pembrolizumab. No treatment-related deaths were reported in the pomalidomide and dexamethasone group. INTERPRETATION: The results from this unplanned, FDA-requested, interim analysis showed that the benefit-risk profile of pembrolizumab plus pomalidomide and dexamethasone is unfavourable for patients with relapsed or refractory multiple myeloma. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co (Kenilworth, NJ, USA).