Management of Mantle Cell Lymphoma in the Era of Novel Oral Agents.

Objectives: To discuss (1) recent and emerging data for pharmacological management of untreated and relapsed/refractory (R/R) mantle cell lymphoma (MCL) with agents approved in the United States, (2) important considerations for toxicity monitoring and management, and (3) preliminary data and ongoing studies for agents in MCL-specific clinical trials. Data Sources: PubMed/MEDLINE, EMBASE, Google Scholar, product labeling, National Comprehensive Cancer Network, American Cancer Society, and ClinicalTrials.gov were searched for studies published between January 1, 2017, and January 31, 2020, and key historical trials. Study Selection and Data Extraction: Relevant studies conducted in humans and selected supporting preclinical data were reviewed. Data Synthesis: MCL is a rare but usually aggressive non-Hodgkin lymphoma that most commonly affects the older population. Traditionally, the treatment of MCL has been determined based on transplant eligibility. Newer data suggest that more tolerable frontline therapy may produce outcomes similar to intensive historical induction regimens, possibly precluding fewer patients from autologous stem cell transplant and producing better long-term outcomes in transplant-ineligible patients. In the R/R setting, novel regimens are improving outcomes and changing the landscape of treatment. Relevance to Patient Care and Clinical Practice: This review summarizes and discusses recent and emerging data for management of newly diagnosed and R/R MCL; key supportive care considerations for agents are also discussed. Conclusions: Recent study results are changing management of MCL. Although these data have complicated the picture of regimen selection, increasingly effective and tolerable therapy and additional anticipated data point to a brighter future for patients with MCL.

Correlation of IL-6 secretion and hyponatremia with the use of CD19+ chimeric antigen receptor T-cells
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BACKGROUND: Various studies have demonstrated that interleukin-6 (IL-6) activates the central magnocellular arginine vasopressin (AVP)-secreting neurons in the brain to produce non-osmotic, non-volume-mediated increases in AVP. The most common toxicity of CD19+ chimeric antigen receptor (CAR) T-cells is cytokine release syndrome, which is related to increased levels of IL-6. This study will evaluate the correlation of IL-6 levels with hyponatremia in patients receiving CD19+ CAR T-cells. MATERIALS AND METHODS: This is a single-center retrospective analysis of adult patients who received CD19+ CAR T-cells for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL). RESULTS: Hyponatremia, defined as a serum sodium (Na) ≤ 135 mEq/L, occurred in 31 (61%) patients. A change in Na > 7 mEq occurred in 32 (63%) patients, and the median lowest Na was 133 mEq/L (interquartile range (IQR): 131 - 136)). There was an inverse linear relationship between IL-6 levels and lowest Na (p = 0.001). Overall, per 10-fold increase in IL-6, Na decreased by an average of 2.68 mEq/L. CONCLUSION: Hyponatremia is common in patients who received CD19+ CAR T-cells. There is an inverse linear relationship between IL-6 levels and nadir Na (p = 0.001). Further studies will be needed to confirm a causative relationship between IL-6 levels and hyponatremia following CD19+ CAR T-cell infusion.

Successful implementation of outpatient R ± DHAX (rituximab, dexamethasone, oxaliplatin, cytarabine) for select patients with lymphoma: a single-center experience.

R ± DHAX has been traditionally administered to inpatient due to the timing of chemotherapy administration and the perceived need for close monitoring of adverse effects. To administer R ± DHAX outpatient, a multidisciplinary task force created clinical and educational guidelines which were implemented through two phases: pilot and expansion. The pilot program determined the feasibility of transitioning R ± DHAX outpatient at a single infusion site. The expansion phase led to a service-wide implementation across all outpatient sites. A total of 40 patients were included, of which 23 patients completed all cycles, outpatient, 12 transitioned inpatient to outpatient administration, and 5 transitioned outpatient to inpatient administration. The success rate of outpatient R ± DHAX administration was 90% (36 patients successfully completed outpatient administration/40 total patients). No cytarabine-related cerebellar or ophthalmic toxicity was reported. Outpatient R ± DHAX saved 192 hospital days. R ± DHAX could be successfully administered outpatient with minimal safety concerns and reduced hospital bed utilization.

Incidence of infectious complications with the combination of bendamustine and an anti-CD20 monoclonal antibody.

Combination of bendamustine (B) and rituximab (R) has been associated with opportunistic infections (OI) in case reports. This retrospective analysis evaluated the incidence, risk factors, and types of infectious complications (IC) in adults with CD20+ non-Hodgkin lymphoma who received ≥2 cycles of B and either R or ofatumumab. Infection data were collected up to 1-year post-B-based treatment. Potential risk factors for IC were assessed using univariate analysis with Fisher's exact test. Four-hundred and sixteen patients were included. Incidence of IC and OI was 20 and 6%, respectively. Viral (n = 19), fungal (n = 1), and Pneumocystis jiroveci pneumonia (n = 5) infections occurred. OI was associated with lack of antimicrobial prophylaxis analysis (p = .048). The incidences of IC and OI with B and anti-CD20 antibody combination at our institution appear lower than those previously reported, possibly due to antimicrobial prophylaxis and G-CSF use.

Clinical pharmacology of oncology agents in older adults: A comprehensive review of how chronologic and functional age can influence treatment-related effects.

Unique challenges exist when managing older adults with cancer. Associations between cancer and age-related physiologic changes have a direct impact on pharmacokinetics and pharmacodynamics of cancer therapies and can affect drug dosing, dose intensity, efficacy, safety and quality of life. The breadth and depth of these issues, however, have not been fully evaluated because the majority of clinical trials have focused on a younger and healthier population. As a consequence, little information is available to support clinicians in making evidence-based decisions regarding treatment with cancer therapies in older adults, especially those over age 75. Prior clinical pharmacology reviews summarized the literature on how age-related physiologic changes can influence and affect conventional and targeted anti-cancer treatments. Our article provides an updated review with expanded information that includes small molecule kinase inhibitors, monoclonal antibodies, immunotherapies, hormonal, conventional, and miscellaneous agents. Additionally, our article integrates how functional age, determined by the geriatric assessment (GA), can also influence treatment-related effects and health outcomes. Broadening cancer therapy trials to capture not only chronologic age but also functional age would allow clinicians to better identify subsets of older adults who benefit from treatment versus those most vulnerable to morbidity and/or mortality.

Current and Investigational Agents Targeting the Phosphoinositide 3-Kinase Pathway.

Prevalent molecular alterations of the phosphoinositide 3-kinase (PI3K) pathway are found on solid tumors and are expressed in leukocytes, making it a desirable target in both solid and hematologic malignancies. In recent years, two agents targeting this pathway have been approved by the United States Food and Drug Administration, idelalisib and copanlisib, with many others under investigation. Due to the off-target effects seen with these agents, those under development have varying isoform specificity that mitigates toxicity. In this review, we attempt to illustrate the varying differences among these agents, both mechanistically as well as highlight differences in their respective adverse effect profiles.