Faiz Anwer

Brentuximab vedotin for treatment of non-Hodgkin lymphomas: A systematic review.

BACKGROUND Brentuximab vedotin (BV) is an antibody-drug conjucate (ADC) comprising a CD30-directed antibody, conjugated to the microtubule-disrupting agent MMAE via a protease cleavable linker. BV is FDA approved for use in relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). There are multiple publications for its utility in other malignancies such as diffuse large B-cell lymphoma (DLBCL), mycosis fungoides (MF), Sézary syndrome (SS), T-cell lymphomas (TCL), primary mediastinal lymphoma (PMBL), and post-transplant lymphoproliferative disorders (PTLD). We believe that BV could potentially provide a strong additional treatment option for patients suffering from NHL. OBJECTIVE Perform a systematic review on the use of BV in non-Hodgkin lymphoma (NHL) and other CD30+ malignancies in humans. DATA SOURCES We searched various databases including PubMed (1946-2015), EMBASE (1947-2015), and Cochrane Central Register of Controlled Trials (1898-2015). ELIGIBILITY CRITERIA Inclusion criteria specified all studies and case reports of NHLs in which BV therapy was administered. INCLUDED STUDIES A total of 28 articles met these criteria and are summarized in this manuscript. CONCLUSION Our findings indicate that BV induces a variety of responses, largely positive in nature and variable between NHL subtypes. With additional, properly powered prospective studies, BV may prove to be a strong candidate in the treatment of various CD30+ malignancies.

Dasatinib-induced pulmonary hypertension in chronic myelogenous leukaemia

A previously healthy 46-year-old woman presented to the outpatient clinic with chronic general weakness for a month. Physical examination showed splenomegaly and complete blood count showed white cell count 346 000/μL, haemoglobin 11.2 g/dL, platelets 336 000/μL with a differential of neutrophils 21%, bands 32%, lymphocytes 8%, monocytes 5%, promyelocytes 22%, myelocytes 11% and blasts 9%. Subsequent bone marrow biopsy showed cellularity of 100% with marked myeloid hyperplasia and blasts of 21%. Cytogenetics demonstrated BCR-ABL1 translocation confirming the diagnosis of chronic myelogenous leukaemia (CML).1 Imatinib was started as an initial treatment, however the patient developed …

Donor origin CAR T cells: graft versus malignancy effect without GVHD, a systematic review

CD19, CD20 chimeric antigen receptor T (CAR T) cell therapy has shown promising results for the treatment of relapsed or refractory hematological malignancies. Best results have been reported in acute lymphoblastic leukemia patients with a complete response rate above 80%. Patients who received donor-derived CAR T cells for the relapsed malignancy after stem cell transplantation (allogenic hematopoietic stem cell transplant) were identified from the published trials. A total of 72 patients from seven studies were treated with donor-derived CAR T cells. Only five out of 72 patients (6.9%) developed graft versus host disease. Use of donor-derived CAR T cell for relapse prophylaxis, minimal residual disease clearance or salvage from relapse is therefore highly effective, and risk of graft versus host disease flare is very low. Side effects include cytokine release syndrome, tumor lysis syndrome, B-cell aplasia along with CNS toxicity.

Role of Maintenance Therapy after High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation in Aggressive Lymphomas: A Systematic Review

Significant uncertainty exists in regard to the efficacy of maintenance therapy after high-dose chemotherapy (HDC) as well as autologous stem cell transplantation (ASCT) for the treatment of patients with aggressive lymphoma. A systematic review was performed to evaluate the effectiveness of post-ASCT maintenance therapy in patients with relapsed/refractory lymphoma. A comprehensive literature search yielded 4476 studies and a total of 42 studies (11 randomized controlled trials [RCT], 9 retrospective comparative studies, and 22 single-arm studies) were included in the systematic review. There was significant heterogeneity in study design, chemotherapeutic regimens, post-ASCT maintenance strategies, patient enrollment criteria, and study endpoints. Our findings suggest that post-ASCT maintenance immune-targeting strategies, including PD-1/PD-L1 blocking antibodies, rituximab, and brentuximab, may improve progression-free survival but not overall survival. Collectively, the results indicate a need for testing new strategies with well-designed and adequately powered RCTs to better address the role of post-ASCT maintenance in relapsed/refractory lymphomas.

Oncolytic reovirus sensitizes multiple myeloma cells to anti-PD-L1 therapy

Adaptive resistance mediated by inhibitory ligands such as PD-L1 has emerged as an important mechanism of malignant cell survival and spurred the development of new agents that disrupt the PD-L1/PD-1 immune checkpoint.1 Analysis of patient specimens from clinical trials of novel immune checkpoint inhibitors indicates that high basal expression of PD-L1 on tumor cells may predict sensitivity to and be necessary to elicit significant clinical benefit from this drug class.2, 3 These data suggest that strategies that increase PD-L1 levels could potentially prime malignant cells with low PD-L1 expression and render them sensitive to anti-PD-1/PD-L1 blockade. In order to investigate this possibility, we first conducted an analysis of basal PD-L1 transcript levels in multiple myeloma (MM) patients

Expanded safety analysis of pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukemia and myelodysplastic syndromes

Expanded safety analysis of pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukemia and myelodysplastic syndromes

Outcome comparison of allogeneic versus autologous stem cell transplantation in transformed low-grade lymphoid malignancies: A systematic review and pooled analysis of comparative studies

Background: Some patients with low-grade lymphoid malignancies develop transformed disease, requiring stem cell transplantation (SCT). SCT outcomes in transformed low-grade lymphoid malignancies may differ from those of nontransformed disease or other aggressive non-Hodgkin lymphomas. We conducted a pooled analysis of the clinical outcomes of allogeneic versus high-dose therapy (HDT) with autologous SCT in adult patients with transformed low-grade lymphoid malignancies. Methods: A PubMed, EMBASE, and Cochrane search yielded 4 comparative studies reporting allogeneic versus HDT with autologous SCT outcomes in adults (age ≥18) with transformed low-grade lymphoid malignancies, including follicular, chronic/small lymphocytic, and marginal zone lymphoma. Risk ratio (RR) and 95% CI were calculated using random-effects models. Results: Rates for overall survival (OS) were 51.0 versus 69.5% (RR = 1.55, 95% CI 1.19-2.02, p = 0.001), rates of relapse were 37.3 versus 35.3% (RR = 1.04, 95% CI 0.70-1.55, p = 0.84), and rates of transplant-related mortality (TRM) were 33.3 versus 7.2% (RR = 4.52, 95% CI 2.75-7.43, p < 0.00001) for allogeneic versus autologous SCT. Previous rituximab treatment, reduced intensity conditioning regimen prior to SCT, or original pathology had no prognostic impact. Conclusion: HDT followed by autologous SCT was associated with lower TRM and a better OS, but there was no difference in relapse versus allogeneic SCT. Autologous SCT may be the better therapeutic option, considering the second chance of allogeneic SCT in the case of relapse.

Waldenström Macroglobulinemia: Review of Pathogenesis and Management

Abstract Waldenström macroglobulinemia (WM) is a low‐grade B‐cell clonal disorder characterized by lymphoplasmacytic bone marrow involvement associated with monoclonal immunoglobulin M. Although WM remains to be an incurable disease with a heterogeneous clinical course, the recent discovery of mutations in the MYD88 and CXCR4 genes further enhanced our understanding of its pathogenesis. Development of new therapies including monoclonal antibodies, proteasome inhibitors, and Bruton tyrosine kinase inhibitors have made the management of WM increasingly complex. Treatment should be tailored to the individual patient while considering many clinical factors. The clinical outcomes are expected to continue to improve, given the emergence of novel therapeutics and better understanding of the underlying pathogenesis.

Retrospective review of intravenous pentamidine for Pneumocystis pneumonia prophylaxis in allogeneic hematopoietic stem cell transplantation

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo‐HSCT) are at risk of numerous opportunistic infections. Pneumocystis jirovecii pneumonia (PJP) is a potentially life‐threatening infection that can develop in immunocompromised individuals. Current prophylaxis for PJP includes trimethoprim‐sulfamethoxazole (TMP‐SMX), dapsone, atovaquone, or inhaled pentamidine (PEN), often with varying breakthrough rates. The use of intravenous (IV) PEN for PJP prophylaxis has been evaluated in pediatric patients.

Blinatumomab-induced donor T-cell activation for post-stem cell transplant-relapsed acute CD19-positive biphenotypic leukemia

Post-stem cell transplantation (SCT) relapsed acute lymphoblastic leukemia (ALL) has extremely poor prognosis with median survival of less than 1 year. Donor lymphocyte infusion, second transplantation, chemotherapy or cytokine treatment have been tried as a salvage regimen without significant clinical benefit. Recently, blinatumomab, a bispecific monoclonal antibody targeting CD3-expressing T cells and CD19-expressing B-cell lineage malignant cells demonstrated promising outcomes in relapsed/refractory ALL patients. Literature on blinatumomab use in biphenotypic ALL along with Philadelphia chromosome positive (Ph(+)) ALL is limited. We report a case of post-SCT relapsed CD19 expressing biphenotypic lymphoblastic leukemia patient who achieved complete remission after blinatumomab treatment and has lasting remission for 1 year.