NCCN Guidelines® Insights: Management of Immunotherapy-Related Toxicities, Version 2.2024.

The NCCN Guidelines for the Management of Immunotherapy-Related Toxicities are intended to provide oncology practitioners with guidance on how to manage the wide-ranging and potentially fatal toxicities that may occur with cancer immunotherapy. The guidelines address immune-related adverse events related to immune checkpoint inhibitors, CAR T-cell therapies, and lymphocyte engagers (which include T-cell-engaging bispecific antibodies). These NCCN Guidelines Insights highlight recent guideline updates pertaining to the management of emerging toxicities related to cancer immunotherapy.

A phase Ib trial of isatuximab, bendamustine, and prednisone in relapsed/refractory multiple myeloma.

Introduction: Patients with triple-class refractory (TCR) multiple myeloma (MM) often need cytoreductive chemotherapy for rapid disease control. Bendamustine is an outpatient-administered, bifunctional alkylator and isatuximab is an anti-CD38 monoclonal antibody with unique cytotoxicity characteristics. We hypothesized that isatuximab-bendamustine-prednisone would be well-tolerated regimen in TCR MM, and conducted single-center, phase Ib, investigator-initiated study.

Clinical whole-genome sequencing and FISH identify two different fusion partners for NUP98 in a patient with acute myeloid leukemia: A case report.

Background: Only rare cases of acute myeloid leukemia (AML) have been shown to harbor a t(8;11)(p11.2;p15.4).

Immune Adjuvant Therapy With Interleukin-7 in a Lymphopenic Patient With Aplastic Anemia and Mucormycosis.

Background: We report the case of a patient with aplastic anemia and pancytopenia on immune-suppressive therapy who developed invasive pulmonary infection with mucormycosis and was treated with immune adjuvant therapy.

Case Summary: Given the patient's profound lymphopenia and progressive invasive mucor despite dual antifungal drug therapy, interleukin (IL)-7, a cytokine that induces lymphocyte activation and proliferation, was instituted and resulted in normalization of absolute lymphocyte counts and was temporally associated with clearance of fungal pathogens and resolution of clinical symptoms.

Conclusion: Patients with life-threatening fungal infections are frequently immune suppressed and immune adjuvant therapies should be considered in patients who are not responding to antifungal drugs and source control.

Evaluation of the Simplified Score to Predict Early Relapse in Multiple Myeloma (S-ERMM) in the MMRF CoMMpass study.

Background: Zaccaria and colleagues recently proposed a new risk score to identify patients at high risk for relapse within 18 months of diagnosis (ER18), the Score for Early Relapse in Multiple Myeloma (S-ERMM). We performed external validation of the S-ERMM using data from the CoMMpass study.

Patients And Methods: Clinical data was obtained from the CoMMpass study.

COVID-19 and Light Chain Amyloidosis, Adding Insult to Injury.

Light chain (AL) amyloidosis is a potentially fatal disease of monoclonal plasma cells that leads to accumulation of light chain amyloid fibrils, organ damage, and the manifestations of clinical disease. Meanwhile, coronavirus disease 2019 (COVID-19) is a disease caused by infection with the severe acute respiratory syndrome coronavirus 2 virus, with the potential to cause severe systemic illness and death. There is significant overlap in the demographics and comorbidities observed in AL amyloidosis and those associated with highest risk for severe morbidity and mortality due to COVID-19.

Cellular Therapy Updates in B-Cell Lymphoma: The State of the CAR-T.

Non-Hodgkin Lymphoma accounts for >460,000 cases and >240,000 deaths globally and >77,000 cases and >20,000 deaths in the U.S. annually, with ~85% of cases being B-cell malignancies.

EGFR/c-Met and mTOR signaling are predictors of survival in non-small cell lung cancer.

Background: EGFR/c-Met activation/amplification and co-expression, mTOR upregulation/activation, and Akt/Wnt signaling upregulation have been individually associated with more aggressive disease and characterized as potential prognostic markers for lung cancer patients.

Methods: Tumors obtained from 109 participants with stage I-IV non-small cell lung cancer (NSCLC) were studied for EGFR/c-Met co-localization as well as for total and active forms of EGFR, c-Met, mTOR, S6K, beta-catenin, and Axin2. Slides were graded by two independent blinded pathologists using a validated scoring system.

GENESIS: Phase III trial evaluating BL-8040 + G-CSF to mobilize hematopoietic cells for autologous transplant in myeloma.

Effective hematopoietic cell transplantation relies upon collecting adequate numbers of CD34 hematopoietic stem cells, typically from peripheral blood. A minimum of ≥2 × 10 CD34 cells/kg are necessary, while transplants of ≥5-6 × 10 CD34 cells/kg are associated with improved hematopoietic recovery. Granulocyte colony stimulating factor (G-CSF) remains the gold standard for hematopoietic stem cell mobilization.

Digital Ischemia and Necrosis: A Rarely Described Complication of Gemcitabine in Pancreatic Adenocarcinoma.

Gemcitabine, alone or in combination with other agents, has become an important part of the standard of care for treatment of both resectable and unresectable/advanced pancreatic adenocarcinoma. Gemcitabine is generally considered to have a favorable toxicity profile, with myelosuppression and hepatotoxicity as the most common adverse effects. There are just two prior published case reports of gemcitabine-associated digital toxicity in the treatment of pancreatic adenocarcinoma, and few case reports when considering all solid tumors.

Oligonucleotides and G-quadruplex stabilizers: targeting telomeres and telomerase in cancer therapy.

Cancer is a leading cause of death worldwide and an estimated 1 in 4 deaths in the United States is due to cancer. Despite recent advances in cancer treatment, adverse effects related to cancer therapy remain a limiting factor for many patients. The ideal cancer treatment would selectively target cancerous cells while sparing normal, healthy cells to offer maximal therapeutic benefit while minimizing toxicity.

Targeting c-Met in melanoma: mechanism of resistance and efficacy of novel combinatorial inhibitor therapy.

Numerous tyrosine kinase inhibitors (TKIs) targeting c-Met are currently in clinical trials for several cancers. Their efficacy is limited due to the development of resistance. The present study aims to elucidate this mechanism of c-Met TKI resistance by investigating key mTOR and Wnt signaling proteins in melanoma cell lines resistant to SU11274, a c-Met TKI.

hnRNP C1/C2 and Pur-beta proteins mediate induction of senescence by oligonucleotides homologous to the telomere overhang.

Background: Experimental disruption of the telomere overhang induces a potent DNA damage response and is the target of newly emerging cancer therapeutics. Introduction of T-oligo, an eleven-base oligonucleotide homologous to the 3'-telomeric overhang, mimics telomere disruption and induces DNA damage responses through activation of p53, p73, p95/Nbs1, E2F1, pRb, and other DNA damage response proteins. ATM (ataxia telangiectasia mutated) was once thought to be the primary driver of T-oligo-induced DNA damage responses; however, recent experiments have highlighted other key proteins that may also play a significant role.

Targeted overexpression of CKI-insensitive cyclin-dependent kinase 4 increases functional β-cell number through enhanced self-replication in zebrafish.

β-Cells of the islet of Langerhans produce insulin to maintain glucose homeostasis. Self-replication of β-cells is the predominant mode of postnatal β-cell production in mammals, with about 20% of rodent β cells dividing in a 24-hour period. However, replicating β-cells are rare in adults.

Thyroid cancer resistance to vitamin D receptor activation is associated with 24-hydroxylase levels but not the ff FokI polymorphism.

Background: The vitamin D receptor (VDR) has been studied as a novel target for cancer therapy in many tissue types as VDR ligands decrease cell proliferation in vitro and decrease tumor growth in vivo in sensitive cells. The objective of this study was to analyze the response to VDR agonist therapy in a panel of validated thyroid cancer cells and assess genetic markers predicting sensitivity and resistance to calcitriol and the noncalcemic analog DP006.

Methods: Thyroid cancer cell lines were analyzed for VDR and RXR protein by Western blot.