Chanan-Khan, Asher

AbstractExtramedullary multiple myeloma is seen in advanced and aggressive disease and occurs due to plasma cell infiltration of sites other than the bone marrow. Myelomatous ascites or pleural effusion is seen in less than 1% of cases and can be differentiated from infectious etiologies based on fluid cytology.

AbstractWaldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is often differentiated from myeloma based on the presence of lytic bone lesions (LBL). However, WM/LPL can present with LBL, and management is poorly understood. We describe a case of an 81‐year‐old woman with LPL who presented with LBL and was successfully treated with chemoimmunotherapy.

Background: Concern exists that the clinical trial populations differ from respective cancer populations in terms of their age distribution affecting the generalizability of the results, especially in underrepresented minorities. We hypothesized that the clinical trials that do not report race are likely to suffer from a higher degree of age disparity. Methods: Food and Drug Administration (FDA) drug approvals from July 2007 to June 2019 were reviewed to identify oncology approvals, and trials with age details were selected. The outcomes studied were the weighted mean difference in age between the clinical trial population and real-world population for various cancers, the prevalence of race reporting and association of age and race reporting with each other. Results: Of the 261 trials, race was reported in 223 (85.4%) of the trials, while 38 trials (14.6%) had no mention of race. Race reporting improved minimally over time: 29 (85.3%) in 2007–2010 vs. 49 (80.3%) in 2011–2014 vs. 145 (85.4%) during the period 2015–2019 (p-value = 0.41). Age discrepancy between the clinical trial population and the real-world population was higher for studies that did not report race (mean difference −8.8 years (95% CI −12.6 to −5.0 years)) vs. studies that did report it (mean difference −5.1 years, (95% CI −6.4 to −3.7 years), p-value = 0.04). Conclusion: The study demonstrates that a significant number of clinical trials leading to cancer drug approvals suffer from racial and age disparity when compared to real-world populations, and that the two factors may be interrelated. We recommend continued efforts to recruit diverse populations.

PURPOSE Among Bruton's tyrosine kinase inhibitors, acalabrutinib has greater selectivity than ibrutinib, which we hypothesized would improve continuous therapy tolerability. We conducted an open-label, randomized, noninferiority, phase III trial comparing acalabrutinib and ibrutinib in patients with chronic lymphocytic leukemia (CLL). METHODS Patients with previously treated CLL with centrally confirmed del(17)(p13.1) or del(11)(q22.3) were randomly assigned to oral acalabrutinib 100 mg twice daily or ibrutinib 420 mg once daily until progression or unacceptable toxicity. The primary end point was independent review committee–assessed noninferiority of progression-free survival (PFS). RESULTS Overall, 533 patients (acalabrutinib, n = 268; ibrutinib, n = 265) were randomly assigned. At the data cutoff, 124 (46.3%) acalabrutinib patients and 109 (41.1%) ibrutinib patients remained on treatment. After a median follow-up of 40.9 months, acalabrutinib was determined to be noninferior to ibrutinib with a median PFS of 38.4 months in both arms (95% CI acalabrutinib, 33.0 to 38.6 and ibrutinib, 33.0 to 41.6; hazard ratio: 1.00; 95% CI, 0.79 to 1.27). All-grade atrial fibrillation/atrial flutter incidence was significantly lower with acalabrutinib versus ibrutinib (9.4% v 16.0%; P = .02); among other selected secondary end points, grade 3 or higher infections (30.8% v 30.0%) and Richter transformations (3.8% v 4.9%) were comparable between groups and median overall survival was not reached in either arm (hazard ratio, 0.82; 95% CI, 0.59 to 1.15), with 63 (23.5%) deaths with acalabrutinib and 73 (27.5%) with ibrutinib. Treatment discontinuations because of adverse events occurred in 14.7% of acalabrutinib-treated patients and 21.3% of ibrutinib-treated patients. CONCLUSION In this first direct comparison of less versus more selective Bruton's tyrosine kinase inhibitors in CLL, acalabrutinib demonstrated noninferior PFS with fewer cardiovascular adverse events.

Objective Outcomes in multiple myeloma (MM) have significantly improved necessitating focus on survivorship. Methods We undertook a web-based survey in collaboration with International Myeloma Foundation (IMF) to explore patient awareness and psycho-physical impacts of MM. The survey was viewed on the IMF website by 1,324 individuals from 32 countries. Results The survey responses were available from 959 individuals, with 62% who completed the survey. Treating doctors were the most frequent source of MM-related information. Only 56% patients admitted full compliance with treatment. Treatment side effects bothered 86% responders, including >50% admitting to pain, peripheral neuropathy and asthenia. Majority (57%) reported some degree of depression, 82% had discontent with their quality of life and only 35% reported being satisfied with their coping mechanisms. Patients ≥65 years of age reported more peripheral neuropathy (p = 0.007) and difficulty with ability to work (p = 0.015). Conclusions We report the prevalence of psychologic, social and physical domains as well as patient-physician relationship dynamics. This knowledge can help improve MM survivorship.Introduction

Importance: Social media is widely used by various segments of society. Its role as a tool of communication by the Public Health Departments in the U.S. remains unknown. Objective: To determine the impact of the COVID-19 pandemic on social media following of the Public Health Departments of the 50 States of the U.S. Design, Setting, and Participants: Data were collected by visiting the Public Health Department web page for each social media platform. State-level demographics were collected from the U.S. Census Bureau. The Center for Disease Control and Prevention was utilized to collect information regarding the Governance of each State’s Public Health Department. Health rankings were collected from “America’s Health Rankings” 2019 Annual report from the United Health Foundation. The U.S. News and World Report Education Rankings were utilized to provide information regarding the public education of each State. Exposure: Data were pulled on 3 separate dates: first on March 5th (baseline and pre-national emergency declaration (NED) for COVID-19), March 18th (week following NED), and March 25th (2 weeks after NED). In addition, a variable identifying the total change across platforms was also created. All data were collected at the State level. Main Outcome: Overall, the social media following of the state Public Health Departments was very low. There was a significant increase in the public interest in following the Public Health Departments during the early phase of the COVID-19 pandemic. Results: With the declaration of National Emergency, there was a 150% increase in overall public following of the State Public Health Departments in the U.S. The increase was most noted in the Midwest and South regions of the U.S. The overall following in the pandemic “hotspots,” such as New York, California, and Florida, was significantly lower. Interesting correlations were noted between various demographic variables, health, and education ranking of the States and the social media following of their Health Departments. Conclusion and Relevance: Social media following of Public Health Departments across all States of the U.S. was very low. Though, the social media following significantly increased during the early course of the COVID-19 pandemic, but it still remains low. Significant opportunity exists for Public Health Departments to improve social media use to engage the public better.

Multiple myeloma (MM) treatment has advanced significantly over the last 2 decades. In most patients, the disease course has been altered from early fatality to chronic morbidity with multiple lines of treatment. The MM treatment paradigm has shifted toward treating patients before end-organ damage occurs. Thus, timeliness of treatment initiation in this era might improve patient outcomes. This is the first report to our knowledge analyzing disparities and trends in treatment timeliness of patients with MM using the National Cancer Database. Multiple factors affected the timing of treatment initiation in MM and disparities were found. We noted that initiation of treatment was delayed in women (odds ratio [OR], 1.15; 95% CI, 1.1 to 1.2) and blacks (OR, 1.21; 95% CI, 1.14 to 1.28; reference, whites) and in patients diagnosed in more recent years (2012-2015; OR, 1.15; 95% CI, 1.1 to 1.22; reference, 2004-2007). Patients were likely to start treatment earlier if they were age ≥ 80 years (OR, 0.83; 95% CI, 0.76 to 0.9; reference, age < 60 years), were uninsured (OR, 0.81; 95% CI, 0.72 to 0.91; reference, private insurance), had Medicaid (OR, 0.87; 95% CI, 0.79 to 0.95; reference, private insurance), were treated in a comprehensive community cancer program (OR, 0.7; 95% CI, 0.65 to 0.77; reference, community cancer program), lived in a location other than the US Northeast, or had a higher Charlson comorbidity score. Patient education and income levels did not affect time to treatment initiation. Particular aspects of these disparities could be explained by our current health care system and insurance rules, whereas others need to be investigated more deeply.

AbstractPurpose:CD38 has emerged as a high-impact therapeutic target in multiple myeloma, with the approval of daratumumab (anti-CD38 mAb). The clinical importance of CD38 in patients with chronic lymphocytic leukemia (CLL) has been known for over 2 decades, although it's relevance as a therapeutic target in CLL remains understudied.Experimental Design:We investigated the biological effects and antitumor mechanisms engaged by daratumumab in primary CLL cells. Besides its known immune-effector mechanisms (antibody-dependent cell-mediated cytotoxicity, complement-dependent death, and antibody-dependent cellular phagocytosis), we also measured direct apoptotic effects of daratumumab alone or in combination with ibrutinib. In vivo antileukemic activity was assessed in a partially humanized xenograft model. The influence of CD38 on B-cell receptor (BCR) signaling was measured via immunoblotting of Lyn, Syk, BTK, PLCγ2, ERK1/2, and AKT.Results:In addition to immune-effector mechanisms; daratumumab also induced direct apoptosis of primary CLL cells, which was partially dependent on FcγR cross-linking. For the first time, we demonstrated the influence of CD38 on BCR signaling where interference of CD38 downregulated Syk, BTK, PLCγ2, ERK1/2, and AKT; effects that were further enhanced by addition of ibrutinib. In comparison to single-agent treatment, the combination of ibrutinib and daratumumab resulted in significantly enhanced anti-CLL activity in vitro and significantly decreased tumor growth and prolonged survival in the in vivo CLL xenograft model.Conclusions:Overall, our data demonstrate the antitumor mechanisms of daratumumab in CLL; furthermore, we show how cotargeting BTK and CD38 lead to a robust anti-CLL effect, which has clinical implications.

Obinutuzumab is used for the treatment of chronic lymphocytic leukemia. So far there are no data of using this for retreatment in patients who have received it previously. We introduced obinutuzumab for the retreatment in a chronic lymphocytic leukemia patient, who had first achieved partial remission with it and eventually relapsed over a course of 2.5 years. After retreatment with single-agent obinutuzumab, the patient achieved a partial remission again within one cycle and continues to maintain the response status. This case is a platform for considering obinutuzumab as a viable option for retreatment of chronic lymphocytic leukemia patients who have received it before, similar to the pattern of use for other anti-CD20 monoclonal antibodies in this disease, including rituximab.