Summary
Immunotherapy is distinct from traditional chemotherapy in that it acts on immune cells rather than cancer cells themselves. Monoclonal antibodies targeting immune checkpoints on T cells – ...CTLA‐4 and PD‐1 – and PD‐L1 on the cells of immune microenvironment are now approved for clinical use in several solid tumors and hematological malignancies. This article provides a general overview of the use of checkpoint inhibitors in hematologic malignancies with a special focus in acute myeloid leukemia.
CD19-targeted chimeric antigen receptor (CAR) T-cell becomes a breakthrough therapy providing excellent remission rates and durable disease control for patients with relapsed/refractory (R/R) ...hematologic malignancies. However, CAR T-cells have several potential side effects including cytokine release syndrome, neurotoxicities, cytopenia, and hypogammaglobulinemia. Infection has been increasingly recognized as a complication of CAR T-cell therapy. Several factors predispose CAR T-cell recipients to infection. Fortunately, although studies show a high incidence of infection post-CAR T-cells, most infections are manageable. In contrast to patients who undergo hematopoietic stem cell transplant, less is known about post-CAR T-cell immune reconstitution. Therefore, evidence regarding antimicrobial prophylaxis and vaccination strategies in these patients is more limited. As CAR T-cell therapy becomes the standard treatment for R/R B lymphoid malignancies, we should expect a larger impact of infections in these patients and the need for increased clinical attention. Studies exploring infection and immune reconstitution after CAR T-cell therapy are clinically relevant and will provide us with a better understanding of the dynamics of immune function after CAR T-cell therapy including insights into appropriate strategies for prophylaxis and treatment of infections in these patients. In this review, we describe infections in recipients of CAR T-cells, and discuss risk factors and potential mitigation strategies.
The prolonged contagious period after viral infection in immunocompromised patients may affect how long precautions will be necessary to reduce further transmission. Replication-competent SARS-CoV-2 ...was detected for up to 61 days in patients who were immunocompromised by treatment for cancer.
Summary
Radiotherapy is potentially an important salvage strategy post‐chimeric antigen receptor T cell therapy (CART), but limited data exist. We reviewed 14 patients treated with salvage radiation ...post‐CART progression (SRT). Most received SRT for first post‐CART relapse (71%) to sites previously PET‐avid pre‐CART (79%). Median overall survival (OS) post‐SRT was 10 months. Post‐SRT, six localized relapses achieved 100% response (3 = complete, 3 = partial), with improved freedom from subsequent relapse (P = 0·001) and OS (P = 0·004) compared to advanced stage relapses. Three were bridged to allogeneic transplantation; at analysis, all were alive/NED. SRT has diverse utility and can integrate with novel agents or transplantation to attempt durable remissions.
Patients who develop steroid-refractory acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation have poor prognosis, highlighting an unmet therapeutic need. In ...this open-label phase 2 study (ClinicalTrials.gov identifier: NCT02953678), patients aged at least 12 years with grades II to IV steroid-refractory aGVHD were eligible to receive ruxolitinib orally, starting at 5 mg twice daily plus corticosteroids, until treatment failure, unacceptable toxicity, or death. The primary end point was overall response rate (ORR) at day 28; the key secondary end point was duration of response (DOR) at 6 months. As of 2 July 2018, 71 patients received at least 1 dose of ruxolitinib. Forty-eight of those patients (67.6%) had grade III/IV aGVHD at enrollment. At day 28, 39 patients (54.9%; 95% confidence interval, 42.7%-66.8%) had an overall response, including 19 (26.8%) with complete responses. Best ORR at any time was 73.2% (complete response, 56.3%). Responses were observed across skin (61.1%), upper (45.5%) and lower (46.0%) gastrointestinal tract, and liver (26.7%). Median DOR was 345 days. Overall survival estimate at 6 months was 51.0%. At day 28, 24 (55.8%) of 43 patients receiving ruxolitinib and corticosteroids had a 50% or greater corticosteroid dose reduction from baseline. The most common treatment-emergent adverse events were anemia (64.8%), thrombocytopenia (62.0%), hypokalemia (49.3%), neutropenia (47.9%), and peripheral edema (45.1%). Ruxolitinib produced durable responses and encouraging survival compared with historical data in patients with steroid-refractory aGVHD who otherwise have dismal outcomes. The safety profile was consistent with expectations for ruxolitinib and this patient population.
•The Janus kinase (JAK)1/2 inhibitor ruxolitinib induced responses in more than half of patients with steroid-refractory aGVHD by day 28.•Ruxolitinib was well tolerated, and the safety profile was consistent with expectations for ruxolitinib and this patient population.
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By late 2018, 2 chimeric antigen receptor T (CAR T) cell products have been approved by US and European regulatory authorities. Tisagenlecleucel (Kymriah, Novartis) is indicated in the treatment of ...patients up to 25 years of age with B‐cell acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, or adult patients with large B‐cell lymphoma relapsed or refractory (r/r) after 2 or more lines of systemic therapy, including diffuse large B‐cell lymphoma (DLBCL) not otherwise specified, high grade B‐cell lymphoma and DLBCL arising from follicular lymphoma. Axicabtagene ciloleucel (Yescarta, Kite) is indicated for the treatment of adult patients with large B‐cell lymphoma relapsed or refractory after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B‐cell lymphoma, high grade B‐cell lymphoma, and DLBCL arising from follicular lymphoma (ZUMA‐1 trial).
This review will offer a practical guide for the recognition and management of the most important toxicities related to the use of the current commercial CAR T cells, and also highlight strategies to diminish these side effects in the future.
Allogeneic hematopoietic cell transplantation involves consideration of both donor and recipient characteristics to guide the selection of a suitable graft. Sufficient high-resolution donor–recipient ...HLA match is of primary importance in transplantation with adult unrelated donors, using conventional graft-versus-host disease prophylaxis. In cord blood transplantation, optimal unit selection requires consideration of unit quality, cell dose and HLA-match. In this summary, the National Marrow Donor Program (NMDP) and the Center for International Blood and Marrow Transplant Research, jointly with the NMDP Histocompatibility Advisory Group, provide evidence-based guidelines for optimal selection of unrelated donors and cord blood units.
Immunocompromised individuals and particularly those with hematologic malignancies are at increased risk for SARS-CoV-2-associated morbidity and mortality due to immunologic deficits that limit ...prevention, treatment, and clearance of the virus. Understanding the natural history of viral infections in people with impaired immunity due to underlying conditions, immunosuppressive therapy, or a combination thereof has emerged as a critical area of investigation during the COVID-19 pandemic. Studies focused on these individuals have provided key insights into aspects of innate and adaptive immunity underlying both the antiviral immune response and excess inflammation in the setting of COVID-19. This review presents what is known about distinct states of immunologic vulnerability to SARS-CoV-2 and how this information can be harnessed to improve prevention and treatment strategies for immunologically high-risk populations.
Vardhana and colleagues discuss how discrete immunological defects in individuals with cancer and other immunosuppressive conditions have informed our understanding of the role of the immune system in protection and toxicity from SARS-CoV-2. They discuss how these immune defects affect the protective impact of vaccination strategies in these individuals and provide insight to limit COVID-19-associated morbidity in this high-risk population.
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