Adriamycin, Vinblastine and Dacarbazine With Immunotherapy Achieves Complete Metabolic Response in a Patient With Classical Hodgkin Lymphoma and Dyskeratosis Congenita.

Primary refractory Hodgkin lymphoma: Limited options and poor survival—but not always

Autologous Peripheral Blood Stem Cell Transplantation in Children with Refractory or Relapsed Lymphoma: Results of Children’s Oncology Group Study A5962

Amahrelis : Adcetris Maintenance after Autologous Stem Cell Transplantation in Hodgkin Lymphoma : A Real Life Study from Sfgmtc and Lysa Groups

Simple SummaryThe standard treatment for Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease is salvage chemotherapy followed by autologous stem cell transplantation (ASCT). With commonly used chemotherapy combinations, 25–30% fail to proceed to ASCT, with poor outcomes. The aim of this retrospective study was to evaluate the efficacy of brentuximab vedotin (BV) and pembrolizumab combination as a bridge to ASCT in R/R HL patients. We retrospectively collected data from 10 patients, 8 male and 2 female, with a median age of 30.7 years. The median follow-up time was 16.5 months, while the median number of received cycles of treatment was 4 (2–7). Eight patients proceeded to ASCT (80%) and seven of them to subsequent BV maintenance, with two early disease progression (PD). The BV and pembrolizumab combination is a very effective bridge treatment to ASCT for high-risk R/R HL patients. Classical Hodgkin lymphoma (HL) patients presenting a relapsed/refractory (R/R) disease are currently managed with salvage chemotherapy followed by autologous stem cell transplantation (ASCT). However, almost 25–30% of these patients fail to achieve a complete response (CR) with standard salvage regimens. In this retrospective study, we evaluated the efficacy of a combination of brentuximab vedotin (BV) and pembrolizumab in a series of HL patients presenting with a high-risk, multi-refractory disease. Patients achieving a Deauville score ≤4 proceeded to ASCT consolidation. After ASCT, patients received BV as maintenance for a total of 16 administrations. We collected data from 10 patients with a median age of 30.7 years. At a median follow-up of 16.5 months, we reported a complete metabolic remission (CMR) in eight patients (80%), with seven patients (70%) directly proceeding to ASCT (the other two patients in CMR are still undergoing treatment). BV consolidation was started in six patients and completed by three patients (one ongoing, two interruption). Two patients (20%) presented a progressive disease (PD) and subsequently died, while the others are still in CMR. The BV and pembrolizumab combination is a very effective bridge treatment to ASCT for high-risk R/R HL patients.

HL-307: A Retrospective Analysis of Brentuximab Vedotin and Pembrolizumab Combination as Salvage Treatment for Patients with Relapsed or Refractory Hodgkin Lymphoma

Real-Life Experience with Brentuximab Vedotin (Adcetris®): the Belgian National Registry

Brentuximab vedotin, an antibody drug conjugate that delivers monomethyl auristatin E into CD-30 expressing cells is FDA approved for the treatment of patients with Hodgkin lymphoma after the failure of autologous stem cell transplantation or at least 2 prior multi-agent chemotherapy regiments. This approval was based on a study that showed an overall response rate of 75% and complete remission in 34%. We present a case of a 24-year-old male with classical nodular sclerosing Hodgkin lymphoma who achieved near complete remission following 5 cycles of brentuximab concurrent with ISRT (involved site radiation therapy) following progression of first-line ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) and subsequent second-line ICE (ifosfamide, carboplatin, etoposide) chemotherapy. This case not only reiterates the efficacy of brentuximab vedotin in the third-line setting but introduces the role of and need for further clinical trials of combined radiotherapy with brentuximab in Hodgkin lymphoma patients following failure of second-line options.

Retrospective Analysis of the Safety and Efficacy of Brentuximab Vedotin in Patients Aged 60 Years or Older with Relapsed or Refractory CD30+ Hematologic Malignancies

Updated Efficacy and Safety Data from the AETHERA Trial of Consolidation with Brentuximab Vedotin after Autologous Stem Cell Transplant (ASCT) in Hodgkin Lymphoma Patients at High Risk of Relapse

Prediction of Progression-Free Survival with Brentuximab Vedotin Therapy for Relapsed Hodgkin Lymphoma: A Retrospective Analysis

Coordinate Regulation of NF-κB Subunit Expression in EBV Negative, but Not EBV Positive, Pediatric Hodgkin's Lymphoma

The PI3K-δ Inhibitor TGR-1202 in Combination with Brentuximab Vedotin (SGN-35) Synergistically Inhibits Tubulin Polymerization and Exerts Potent Antitumor Effects in NOD/SCID Mice with Hodgkin Lymphoma Cell Line Xenografts

Introduction: The combination of brentuximab vedotin (BV) with AVD chemotherapy followed by 30 Gy involved-site radiotherapy (ISRT) for the treatment of early stage, unfavorable risk Hodgkin lymphoma (HL) has demonstrated promising efficacy and an acceptable safety profile in the first cohort of this pilot study (Kumar et al., Blood, 2016). In cohort 2, we evaluated whether the reduced dose of ISRT to 20 Gy decreased RT-related toxicity while maintaining efficacy. Methods: Patients received 4 cycles of BV 1.2 mg/kg with AVD chemotherapy every 2 weeks followed by 30 Gy ISRT in cohort 1 and 20 Gy ISRT in cohort 2. Eligible patients had untreated stage I/II classical HL with any of the following unfavorable risk factors: bulky disease (maximal transverse or coronal diameter > 7 cm on CT), elevated ESR, extranodal involvement, >2 lymph node sites, or infradiaphragmatic disease. Patients with stage IIB disease with disease bulk or extranodal involvement were eligible. PET/CT after 2 and 4 cycles and ISRT were interpreted with the Deauville 5-point scale (negative = 1-3). The primary endpoint of cohort 2 was to evaluate preliminary efficacy by complete response (CR) rate. Results: In cohort 2, 29 patients were enrolled from May 2015 to October 2016 with median age of 33 (range, 19-55), 100% stage II, 69% with disease bulk (>7 cm), 38% elevated ESR, 38% B-symptoms, 21% extranodal involvement, 69% >2 involved lymph node sites, and 3% infradiaphragmatic disease. Twenty patients (69%) had bulky anterior mediastinal masses, ranging from 7 to 17.3 cm. Nine patients (31%) had advanced stage disease by the GHSG criteria: IIBX (n = 7) and IIBXE (n = 2). In cohort 2, 90% and 93% of patients achieved a negative PET scan after 2 and 4 cycles of therapy, respectively. Of the 2 patients with positive PET-4 scans, one underwent a biopsy that was negative for HL, and the other had residual FDG-uptake in a location not amenable to biopsy. Both patients received ISRT. The 25 patients who completed combined modality therapy (CMT) have achieved CRs. To date, the duration of remission ranges from 2 to 13 months, and no relapses have occurred. The efficacy is similar across cohorts 1 and 2 with interim PET negative rates of ≥90%, and all patients who completed CMT have achieved a CR (Figure 1). In cohort 1, 2 patients had biopsy-proven primary refractory HL after 4 cycles of chemotherapy, and in cohort 2, there have been no treatment failures. Conclusion: BV + AVD x 4 cycles followed by 20 Gy ISRT has promising preliminary efficacy for the treatment of early stage, unfavorable risk HL, including a high proportion of patients with bulky disease. As with 4 cycles of escalated BEACOPP tested in the GHSG HD11 clinical trial, 20 Gy ISRT may be adequate consolidation after BV + AVD x 4 cycles. We recommend that BV + AVD x 4 + 20 Gy ISRT is studied in a larger, randomized prospective study for early stage, bulky HL. Updated response data for all patients will be presented at the meeting. Keywords: brentuximab vedotin; Hodgkin lymphoma (HL)

A Retrospective Analysis of Brentuximab Vedotin and Pembrolizumab Combination As Salvage Treatment for Patients with Relapsed or Refractory Hodgkin Lymphoma

Homozygous and Compound Heterozygous Mutations in the Telomerase Reverse Transcriptase Gene in Two Families with Spontaneous Dyskeratosis Congenita and Idiopathic Aplastic Anemia.