Natalie S. Grover

A phase II trial of bendamustine in combination with rituximab in older patients with previously untreated diffuse large B‐cell lymphoma

Bendamustine in combination with rituximab (BR) has been associated with high response rates and acceptable toxicity in older patients with relapsed/refractory diffuse large B‐cell lymphoma (DLBCL). Evaluation of BR is warranted in the front‐line setting for DLBCL patients not eligible for anthracyclines or for the elderly. In this phase II study, we enrolled DLBCL patients aged ≥65 years who were poor candidates for R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) to determine the efficacy and safety of BR in previously untreated stage II–IV DLBCL. Twenty‐three patients were enrolled with a median age of 80 years. 52% of patients presented with poor functional status (Eastern Cooperative Oncology Group performance score of ≥2). The overall response rate was 78% with 12 complete responses (52%). At a median follow up of 29 months, the median overall survival was 10·2 months and the median progression‐free survival was 5·4 months. The most common grade 3/4 adverse events were haematological. Combination therapy with BR demonstrates high response rates as front‐line therapy in frail older patients with DLBCL, but survival rates were low. BR should be used with caution in future clinical trials involving older DLBCL patients with poor functional status.

Novel Targeted Agents in Hodgkin and Non-Hodgkin Lymphoma Therapy

There has been a recent emergence of novel targeted agents for treatment of Hodgkin and non-Hodgkin lymphoma. In particular, antibodies and antibody-drug conjugates directed against surface antigens, agents that block immune checkpoint pathways, and small molecule inhibitors directed against cell signaling pathways have shown significant promise in patients with relapsed and refractory disease and in the frontline setting. With the development of these new therapies, cytotoxic chemotherapy may be avoided entirely in some clinical settings. This review will present the latest information on these novel treatments in Hodgkin and non-Hodgkin lymphoma and will discuss both recently approved agents as well as drugs currently being studied in clinical trials.

Young Men With Cancer Experience Low Referral Rates for Fertility Counseling and Sperm Banking

PURPOSE With improved cancer survival rates and the current trend of delaying parenthood, fertility is a growing issue among cancer patients. The purpose of this study was to evaluate the incidence of fertility counseling and sperm banking in reproductive-age male cancer patients and to assess factors that influence counseling and banking. MATERIALS AND METHODS Male patients ages 13 to 50 years who received a new cancer diagnosis from January 1, 2013, to May 1, 2015, and planned to initiate curative chemotherapy at our center were identified. Documentation of fertility counseling and sperm cryopreservation was abstracted from the medical record. Univariable and multivariable logistic regression modeling was used to examine variables associated with fertility counseling and sperm banking. RESULTS Of 201 patients who fit the study criteria, 59 (29%) received fertility counseling and 23 (11%) attempted sperm banking. All patients who banked sperm had documentation of fertility counseling. Younger patients were significantly more likely to be counseled, with mean ages of 27.4 and 40.4 years for counseled and noncounseled patients, respectively (P < .001). Among counseled patients, those with a lower median income (P = .038) or who had Medicaid or no insurance (P = .042) were less likely to bank sperm. In a multivariable logistic regression model, older age (5-year odds ratio, 0.61; P < .001) and presence of comorbidities (odds ratio, 0.15; P = .03) remained significantly associated with a lower counseling rate. CONCLUSION There is a low rate of fertility counseling and referral for sperm banking in young men with cancer receiving chemotherapy. Further work is needed to develop interventions to improve fertility counseling rates and opportunities for sperm banking.

Bortezomib in combination with dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) induces long-term survival in patients with plasmablastic lymphoma: a retrospective analysis

Abstract Plasmablastic lymphoma (PBL) is a rare and aggressive form of B-cell non-Hodgkin lymphoma. This subtype of lymphoma has a post-germinal center cell-of-origin called the plasmablast, and the immunophenotype is more consistent with that of a plasma cell than a lymphocyte. Because of these unique features, PBL is notoriously difficult to treat. Case reports and small reviews have evaluated the addition of agents directed against plasma cell disorders in combination with traditional lymphoma-directed regimens. We describe the largest case series to date, with the longest follow-up, evaluating bortezomib in combination with etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (V-EPOCH) for the treatment of PBL. Our results show that this is a safe and effective regimen with an overall and complete response rate of 100% and 2-year overall survival of 50%.

Complex karyotype in patients with mantle cell lymphoma predicts inferior survival and poor response to intensive induction therapy

Risk stratification of newly diagnosed patients with mantle cell lymphoma (MCL) primarily is based on the MCL International Prognostic Index (MIPI) and Ki‐67 proliferative index. Single‐center studies have reported inferior outcomes in patients with a complex karyotype (CK), but this remains an area of controversy.

Deferred treatment is a safe and viable option for selected patients with mantle cell lymphoma.

Abstract Prospective identification of candidates for deferred therapy is not standardized and many patients receive immediate therapy regardless of risk. We conducted a retrospective, multi-center cohort analysis of MCL patients with comprehensive clinical data to examine the use and safety of deferred therapy for newly diagnosed patients. Previously untreated patients ≥18 years-old with MCL diagnosed in 1993–2015 at five academic sites were included. Of 395 patients, 72 (18%) received deferred therapy (defined as receipt of first treatment >90 days following initial diagnosis). Patients receiving deferred therapy were more likely to have an ECOG performance status of 0 (67 versus 44% p = .001), have no B symptoms (83 versus 65% p = .003) and have normal LDH levels at diagnosis (87 versus 55% p < .001). In multivariable analysis, deferred therapy was not associated with a significant difference in OS (HR 0.64: 95% CI 0.22–1.84, p = .407).

Hodgkin Lymphoma With Multiple Autoimmune Disorders: Case Report and Review of the Literature

This is a case report and review of the literature of Hodgkin lymphoma (HL) and multiple autoimmune disorders. We report a case of a patient who presented initially with refractory immune thrombocytopenia (ITP) and was subsequently diagnosed with HL and was also found to have other autoimmune disorders (Hashimoto thyroiditis and primary biliary cirrhosis [PBC]). Her ITP and PBC improved with therapy for HL. In some patients with autoimmune disorders such as ITP and PBC presenting around the time of HL diagnosis, these conditions may be paraneoplastic and may improve with lymphoma therapy. For patients presenting with autoimmune disease and lymphadenopathy, it is important to have a high index of suspicion for HL and pursue an excisional biopsy, if feasible; a suboptimal biopsy could result in a missed diagnosis.

Targeting Immune System Alterations in Hodgkin Lymphoma

Purpose of ReviewThis review discusses novel immunotherapeutic approaches to treat Hodgkin lymphoma (HL), specifically PD-1 inhibitors and cellular immunotherapy.Recent FindingsPD-1 inhibitors have shown promising results in the treatment of relapsed or refractory HL, leading to FDA approval of nivolumab and pembrolizumab, although complete remissions are rare. Chimeric antigen receptor T cells directed against CD30 have been investigated with preliminary clinical trials showing minimal toxicities and some responses in heavily pre-treated patients with HL.SummaryHL is unique as it consists of a small percentage of malignant cells (Hodgkin Reed Sternberg cells) surrounded by an inflammatory microenvironment which promotes tumor growth and suppresses immune responses, making it an ideal target for immunotherapeutic approaches, such as PD-1 inhibitors and cellular immunotherapy. Current research is focused on overcoming barriers to efficacy via rational combinations that overcome resistance to therapy.

Patient perspectives on physical function after allogeneic hematopoietic stem cell transplantation: a qualitative study

Hematopoietic stem cell transplantation (HSCT) is a life-saving treatment for some patients with aggressive hematologic malignancies, but many recipients develop temporary or persistent impairments in physical functioning.1 There is increasing evidence that impaired physical functioning is prognostic for survival in transplant recipients.2, 3 Furthermore, preserved physical functioning is necessary for patients to live independently and achieve goals that support their overall quality of life.