Redefining Precision Management of r/r Large B-Cell Lymphoma: Novel Antibodies Take on CART and BMT in the Quest for Future Treatment Strategies.

The treatment paradigms for patients with relapsed large B-cell lymphoma are expanding. Chimeric antigen receptor technology (CAR-T) has revolutionized the management of these patients. Novel bispecific antibodies and antibody-drug conjugates, used as chemotherapy-free single agents or in combination with other novel therapeutics, have been quickly introduced into the real-world setting. With such a paradigm shift, patients have an improved chance of better outcomes with unpredictable complete remission rates. Additionally, the excellent tolerance of new antibodies targeting B-cell lymphomas is another motivation to broaden its use in relapsed and refractory patients. With the increasing number of approved therapy approaches, future research needs to focus on optimizing the sequence and developing new combination strategies for these antibodies, both among themselves and with other agents. Clinical, pathological, and genetic risk profiling can assist in identifying which patients are most likely to benefit from these costly therapeutic options. However, new combinations may lead to new side effects, which we must learn to deal with. This review provides a comprehensive overview of the current state of research on several innovative antibodies for the precision management of large B-cell lymphoma. It explores various treatment strategies, such as CAR-T vs. ASCT, naked antibodies, antibody-drug conjugates, bispecific antibodies, and bispecific T-cell engagers, as well as discussing the challenges and future perspectives of novel treatment strategies. We also delve into resistance mechanisms and factors that may affect decision making. Moreover, each section provides a detailed analysis of the available literature and ongoing clinical trials.

Understanding the differences in outcome between CART studies as second-line treatment in aggressive lymphoma.

Patients with refractory/early relapsed aggressive lymphomas belong to the most difficult-to-treat patients with hematological neoplasia. The prognosis of such patients is poor and novel treatment approches are urgently needed. Autologous chimeric antigen receptor T-cell therapy is a promising new therapy option that is approved after the failure of two lines of chemotherapy. Recently, the results of three different CART studies (ZUMA-7, TRANSFORM, and BELINDA) were published. Two of them were positive and one was negative, which created a mix of disappointment, confusion, and irritation. In this article, we are analyzing the data of all three trials and shed light on the differences between the studies which may facilitate an easier understanding of the results and relevance of CART in aggressive large B-cell lymphoma.

Outpatient fractionated ICE protocol in relapsed/refractory lymphomas: Efficacy and safety.

METHODS: In this retrospective trial, we analyzed data of patients with relapsed/refractory lymphoma who received outpatient fractionated ICE between 2011-2017 at a tertiary care center. The three weekly ICE protocol consisted of: ifosfamide 1500 mg/m2 infused over 2 h on days 1-3, carboplatin (5 AUC) on day 1, and etoposide 100 mg/m2 on days 1-3. Rituximab 375 mg/m2 was given to patients with CD20 positive B cell Non-Hodgkin lymphoma. RESULTS: Total of 89 patients were included in this research project. Majority of patients had Hodgkin lymphoma (64%). Mean number of ICE cycles received was 2.5. Complete remission and partial remission rates for primary refractory (62.9%) and non-primary refractory (36.4%) disease were 10.5% and 26.3% versus 41.9% and 29.0% respectively. Event free survival rate was 14.5 months (95% CI 7.7-28.0) and overall survival rate 88.7 months (95% CI 48.1-NR). Grade 3 hematological toxicities were documented in 19.1% of patients with 10.1% experiencing neutropenia and 9% thrombocytopenia. 5.6% had febrile neutropenia. CONCLUSIONS: Our study included, to our knowledge, the largest number of patients treated with outpatient fractionated ICE. Results demonstrated that this regimen might be a reasonable replacement for classic ICE regimen in many patients with lymphoma. It has a favorable safety profile. However, patients with primary refractory lymphomas need more effective regimens.

Impact of granulocyte-colony stimulating factor on docetaxel-induced febrile neutropenia in patients with breast cancer.

BACKGROUND: Febrile neutropenia (FN) is a life-threatening complication of Docetaxel-based chemotherapy regimens (DBRs). Prophylactic granulocyte-colony stimulating factor (G-CSF) can reduce the risk of FN. This study investigated the effect of G-CSF on FN in patients receiving DBRs for breast cancer. METHODS: Patients treated between 2015 and 2017 were identified from the hospital's pharmacy database and their medical records were examined retrospectively. Data from patients' first four cycles of DBR were collected. FN rate, FN associated length of hospital stay (FN-LOS), and chemotherapy dose modification/delay due to FN were compared between patients who did (G-CSF group) or did not (non-GCSF group) receive prophylactic G-CSF. RESULTS: Of the 276 included patients, 83.3% received a DBR as adjuvant or neoadjuvant therapy, and 50% received docetaxel as combination therapy. Prophylactic G-CSF was administered with the first cycle of a DBR in 69.9% of patients who were significantly less likely to experience FN compared to the non-G-CSF group (6.2% vs. 15.7%; odds ratio: 0.36 [95% CI: 0.16-0.82]; p = 0.020). Collectively and after the 4 DBR treatment cycles, FN rate (4.8 vs. 8.5; odds ratio: 0.54 [95% CI: 0.30-0.97]; p = 0.043) and the mean FN-LOS (3.55 vs. 5.28 days; t = -2.22; p = 0.037) were reduced in the G-CSF group. There was no difference in DBR dose delay/reduction between both groups in cycles 2-4. CONCLUSION: In patients receiving DBRs for breast cancer, prophylactic G-CSF significantly reduced both the rate of FN and duration of hospitalization for FN.

Saudi Lymphoma Group's Clinical Practice Guidelines for Diagnosis, Management and Follow-up of Patients with Various Types of Lymphoma during the Coronavirus Disease 2019 Pandemic.

The Saudi Lymphoma Group had previously published recommendations on the management of the major subtypes of lymphoma. However, the effect the currently ongoing coronavirus disease 2019 (COVID-19) pandemic has on the management of patients with lymphoma has been paramount. Therefore, the Saudi Lymphoma Group has decided to provide clinical practice guidelines for the diagnosis, management and follow-up of patients with various types of lymphoma during the COVID-19 pandemic.

The AUGMENT study: Lenalidomide in indolent lymphoma balance the imbalance!

Follicular lymphoma is the most common form of indolent Non-Hodgkin Lymphoma and characterized by repeated relapses. Follicular lymphoma (FL) tissue was found to have association between malignant cells and benign immune cells represented in the surrounded microenvironment. Lenalidomide, an immunomodulator, is affecting this microenvironment and demonstrated relevant clinical activity in phase III trials in patients with FL lymphoma. The AUGMENT trial resulted in a better PFS with lenalidomide and rituximab than rituximab and placebo in patients with relapsed/refractory FL and marginal zone lymphoma. However, there are some concerns around the study. The following article is discussing some of these concerns.

Diagnosis and management of follicular lymphoma: A comprehensive review.

Follicular Lymphoma (FL) is an indolent lymphoma and may have various clinical courses. Worldwide, FL is the second most common non-Hodgkin lymphoma (NHL) type after diffuse large B-cell lymphoma. In this review article, the author is discussing relevant diagnostic tools, prognostic factors, and updated study results on the management of patients with newly diagnosed and relapsed/refractory FL. Controversies in the treatment, maintenance therapy, stem cell transplantation, and novel treatment approaches will be comprehensively discussed.

Allogeneic hematopoietic stem cell transplantation in r/r Hodgkin lymphoma after treatment with checkpoint inhibitors: Feasibility and safety.

OBJECTIVES: Relapsed cHL patients after autologous hematopoietic stem cell transplantation (HSCT) with treatment-sensitive disease are potential candidates for curative allogeneic HSCT. However, there are some concerns around performing such procedure after checkpoint inhibitors (CPIs). METHODS: We collected published data of patients undergoing allogeneic HSCT after treatment with CPIs (cohort 1). Abstracts of recent conferences (2015-2017; ASCO, ASH, EBMT, ASBMT) were also included. Results were compared with safety of recent studies (2015-2018) with allogeneic HSCT without CPIs (cohort 2). RESULTS: A total of 272 records were screened. After exclusion of duplications, cohorts 1 and 2 included each 6 publications with 122 and 978 patients, respectively. Grade 3-4 acute GVHD in cohort 1 was found in 28% vs 8% in cohort 2 (P = 0.02). Chronic GVHD was observed in 26% vs 29%, respectively. NRM was 15% which remained relatively stable after 6 months of allogeneic HSCT vs 19% in cohort 2. CONCLUSIONS: This is the largest pooled analysis of its kind published so far. Our results suggest that allogeneic HSCT after CPIs is feasible and not associated with higher mortality. However, careful consideration should be given for prevention, early detection, and effective treatment of GVHD in these cases. Additional prospective studies are needed for further clarification.

Nivolumab induces impressive responses in relapsed/refractory classic Hodgkin lymphoma: Single institutional experience.

OBJECTIVES: Cancer can escape the immune system through different mechanisms. One such mechanism is the expression of program death ligand-1 which binds to PD-1 receptor on activated T cells, subsequently leading to inhibition of the immune response against cancer cells. Nivolumab is a novel antibody that binds to PD-1 and prevents such immune tolerance. Two recently published controlled clinical trials confirmed the clinical efficacy of single-agent nivolumab in pretreated patients with classical Hodgkin lymphoma. PATIENTS AND METHODS: We treated 10 heavily pretreated patients with classical Hodgkin lymphoma with the new novel PD-1 inhibitor nivolumab. We report on the outcome and safety of this agent in these patients. RESULTS: After four cycles, the response rate was 80%. Seven of 10 gained complete metabolic remission. No serious adverse events were observed. The available literature is being reviewed. CONCLUSIONS: Pretreated classical Hodgkin lymphoma is amenable to novel immunotherapy. Nivolumab induces clinically meaningful responses with excellent tolerability. The drug enriches our treatment options by reviving the response of the immune system against cancer. Further controlled studies are needed to determine the effectiveness on a large patient cohort.

Program death inhibitors in classical Hodgkin's lymphoma: a comprehensive review.

Cancer cells are able to induce immune system tolerance through different mechanisms. Recent achievements in the understanding of tumor microenvironment, invasion, and metastasizing have contributed to accelerated drug developments and approvals. Hodgkin lymphoma (HL) cells are the minority in a lymphocyte-rich microenvironment of HL tissue. The program death-1 (PD-1)/PD-ligand-1 checkpoint is one of the known effective pathways in classical HL to escape the immune system cells. The approval of PD-1 inhibitors in different cancer types with exciting response rates is truly revolutionizing our treatment armamentarium against cancer in general and classical HL in specific. Although the disease is one of the most curable tumors, we still need better outcome with more gentle treatment, especially for relapsed and refractory (r/r) patients. In this article, we review the current literature on immune checkpoint inhibitors and currently ongoing studies with nivolumab and pembrolizumab in r/r classical HL.