Therapeutic recommendations for early stage Hodgkin lymphomas.

Combined modality treatment has been the standard option for the treatment of early stage Hodgkin lymphoma for several decades. Because of the high success rate and the risk of late toxicities, recent clinical trials have focused on reducing the treatment burden. Field and dose of radiotherapy, and number of cycles of chemotherapy have been successfully reduced, particularly for favourable early stage patients. However, the impact of these treatment reductions on the rate of secondary malignancies remains still unclear. Positron emission tomography-computed tomography (PET-CT) scanning has emerged as a very important tool for disease staging and end of treatment assessment. Interestingly, a PET performed after 2 cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine) has been correlated with final outcome and was recently evaluated in a randomized clinical trial to evaluate individualized therapy based on PET response after 2 or 3 cycles of ABVD. These trials aimed to identify good prognosis (early PET-negative) patients who could be spared radiotherapy, but also patients with a bad prognosis (early PET-positive) who need more intensive treatment. More recently, new drugs, such as brentuximab vedotin and checkpoint inhibitors, have shown efficacy in relapsed/refractory patients and are currently under evaluation in early stage patients.

Complete Remission in a TEMPI Syndrome Treated with a Daratumumab, Lenalidomide, and Dexamethasone-Based Regimen: A Case Report.

Introduction: TEMPI syndrome is a rare and acquired condition which is characterized by five classical features: telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, and intrapulmonary shunting. The classical treatment is based on bortezomib which can achieve variable responses. Relapse or refractory disease may occur, so other treatment strategies can be proposed. Case Presentation: We describe the case of a 54-year-old male followed for a refractory TEMPI syndrome who achieved complete remission after a second-line therapy composed of daratumumab-, lenalidomide-, and dexamethasone-based regimen (DLd). He achieved a complete remission with dramatic improvement of his renal function, restitution of a normal blood oxygen, and disappearance of polycythemia. Conclusion: This case highlights the effectiveness of an association of DLd to treat refractory TEMPI syndrome. We also provide arguments for an association between TEMPI syndrome and monoclonal gammopathy of renal significance.

Cryptosporidiosis, an Uncommon Complication after Allogeneic Stem-Cell Transplantation.

Parasitic infections by Cryptosporidium species are rare but can be life-threatening disease after allogeneic stem-cell transplantation (allo-SCT). Here, we reported a case of cryptosporidiosis occurring after a reduced-intensity conditioning and allo-SCT in a 64-year-old farmer with diffuse large B-cell lymphoma. Around day 70 after allo-SCT, he presented with diarrhea attributed to graft-versus-host disease (GvHD) and was treated with immunosuppressive therapy. Due to the patient's worsening clinical condition, a biopsy review was performed, revealing evidence of cryptosporidiosis. Therefore, immunosuppressive therapy was progressively decreased, and antimicrobial therapy including paromomycin and azithromycin was initiated. Following an increase in diarrhea, a second-line treatment with nitazoxanide was administered, resulting in gradual improvement of symptoms. However, recurrence of cryptosporidiosis occurred despite treatment with paromomycin 6 months after transplant and after an episode of GvHD recurrence and colic cytomegalovirus reactivation. Antiparasitic treatment was stopped and azithromycin and rifaximine were started. Immunosuppressive therapy was also reduced. The good clinical evolution allowed for the cessation of all medications. In conclusion, Cryptosporidium infection can complicate allo-SCT and be mistaken for GvHD at the clinical and histologic levels. Early and accurate diagnosis is all the more important as the therapeutic approach for the two conditions is opposite: reduction versus intensification of immunosuppressive therapy. Nitazoxanide, paromomycin, and azithromycin are the first therapeutic options.

Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results.

Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody. In the ongoing phase 2 MagnetisMM-3 trial, patients with relapsed or refractory multiple myeloma received subcutaneous elranatamab once weekly after two step-up priming doses. After six cycles, persistent responders switched to biweekly dosing. Results from cohort A, which enrolled patients without prior BCMA-directed therapy (n = 123) are reported. The primary endpoint of confirmed objective response rate (ORR) by blinded independent central review was met with an ORR of 61.0% (75/123); 35.0% ≥complete response. Fifty responders switched to biweekly dosing, and 40 (80.0%) improved or maintained their response for ≥6 months. With a median follow-up of 14.7 months, median duration of response, progression-free survival and overall survival (secondary endpoints) have not been reached. Fifteen-month rates were 71.5%, 50.9% and 56.7%, respectively. Common adverse events (any grade; grade 3-4) included infections (69.9%, 39.8%), cytokine release syndrome (57.7%, 0%), anemia (48.8%, 37.4%), and neutropenia (48.8%, 48.8%). With biweekly dosing, grade 3-4 adverse events decreased from 58.6% to 46.6%. Elranatamab induced deep and durable responses with a manageable safety profile. Switching to biweekly dosing may improve long-term safety without compromising efficacy. ClinicalTrials.gov identifier: NCT04649359 .

Long-term overall survival and toxicities of ABVD vs BEACOPP in advanced Hodgkin lymphoma: A pooled analysis of four randomized trials.

PURPOSE: We explored the potential overall survival (OS) benefit of bleomycin, etoposide, doxorubicin (Adriamycin), cyclophosphamide, vincristine (Oncovin), procarbazine, and prednisone (BEACOPP) over doxorubicin (Adriamycin), bleomycin, vinblastine, and dacarbazine (ABVD) in a pooled analysis of four randomized trials. PATIENTS AND METHODS: Primary objective was to evaluate the OS impact of BEACOPP using individual patient data. Secondary objectives were progression-free survival (PFS), secondary cancers, and use of autologous stem cell transplantation (ASCT). RESULTS: About 1227 patients were included. The 7-year OS was 84.3% (95% CI 80.8-87.2) for ABVD vs 87.7% (95% CI 84.5-90.2) for BEACOPP. Two follow-up periods were identified based on survival curves and hazard ratio (HR) over time. For the first 18 months, there was no difference. For the second period of ≥18 months, ABVD patients had a higher death risk (HRABVD vs BEACOPP  = 1.59; 95% CI 1.09-2.33). A Cox model stratified by trial and evaluating the effect of treatment and International Prognostic Index (IPI) score as fixed effects showed that both were statistically significant (treatment, P = .0185; IPI score, P = .0107). The 7-year PFS was 71.1% (95% CI 67.1-74.6) for ABVD vs 81.1% (95% CI 77.5-84.2) for BEACOPP (P < .001). After ABVD, 25 secondary cancers (4.0%) were reported with no myelodysplasia (MDS)/acute myeloid leukemia (AML) compared to 36 (6.5%) after BEACOPP, which included 13 patients with MDS/AML. Following ABVD, 86 patients (13.8%) received ASCT vs 39 (6.4%) for BEACOPP. CONCLUSIONS: This analysis showed a slight improvement in OS for BEACOPP and confirmed a PFS benefit. Frontline use of BEACOPP instead of ABVD increased secondary leukemia incidence but halved the requirement for ASCT.