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Quality of life analyses in patients with multiple myeloma: results from the Selinexor (KPT-330) Treatment of Refractory Myeloma (STORM) phase 2b study
Tremblay, Gabriel; Daniele, Patrick; Breeze, Janis; Li, Lingling; Shah, Jatin; Shacham, Sharon; Kauffman, Michael; Engelhardt, Monika; Chari, Ajaj; Nooka, Ajay; Vogl, Dan; Gavriatopoulou, Maria; Dimopoulos, Meletios-Athanasios; Richardson, Paul; Biran, Noa; Siegel, David; Vlummens, Philip; Doyen, Chantal; Facon, Thierry; Mohty, Mohamad; Meuleman, Nathalie; Levy, Moshe; Costa, Luciano; Hoffman, James E; Delforge, Michel; Kaminetzky, David; Weisel, Katja; Raab, Marc; Dingli, David; Tuchman, Sascha; Laurent, Frenzel; Vij, Ravi; Schiller, Gary; Moreau, Philippe; Richter, Joshua; Schreder, Martin; Podar, Klaus; Parker, Terri; Cornell, Robert Frank; Lionel, Karlin; Choquet, Sylvain; Sundar, Jagannath
BACKGROUND:Selinexor is an oral, selective nuclear export inhibitor. STORM was a phase 2b, single-arm, open-label, multicenter trial of selinexor with low dose dexamethasone in patients with penta-exposed relapsed/refractory multiple myeloma (RRMM) that met its primary endpoint, with overall response of 26% (95% confidence interval [CI], 19 to 35%). Health-related quality of life (HRQoL) was a secondary endpoint measured using the Functional Assessment of Cancer Therapy - Multiple Myeloma (FACT-MM). This study examines impact of selinexor treatment on HRQoL of patients treated in STORM and reports two approaches to calculate minimal clinically important differences for the FACT-MM. METHODS:FACT-MM data were collected at baseline, on day 1 of each 4-week treatment cycle, and at end of treatment (EOT). Changes from baseline were analyzed for the FACT-MM total score, FACT-trial outcome index (TOI), FACT-General (FACT-G), and the MM-specific domain using mixed-effects regression models. Two approaches for evaluating minimal clinically important differences were explored: the first defined as 10% of the instrument range, and the second based on estimated mean baseline differences between Eastern Cooperative Oncology Group performance status (ECOG PS) scores. Post-hoc difference analysis compared change in scores from baseline to EOT for treatment responders and non-responders. RESULTS:Eighty patients were included in the analysis; the mean number of prior therapies was 7.9 (standard deviation [SD] 3.1), and mean duration of myeloma was 7.6 years (SD 3.4). Each exploratory minimal clinically important difference threshold yielded consistent results whereby most patients did not experience HRQoL decline during the first six cycles of treatment (range: 53.9 to 75.7% for the first approach; range: 52.6 to 72.9% for the second). Treatment responders experienced less decline in HRQoL from baseline to EOT than non-responders, which was significant for the FACT-G, but not for other scores. CONCLUSION/CONCLUSIONS:The majority of patients did not experience decline in HRQoL based on minimal clinically important differences during early cycles of treatment with selinexor and dexamethasone in the STORM trial. An anchor-based approach utilizing patient-level data (ECOG PS score) to define minimal clinically important differences for the FACT-MM gave consistent results with a distribution-based approach. TRIAL REGISTRATION/BACKGROUND:This trial was registered on ClinicalTrials.gov under the trial-ID NCT02336815 on January 8, 2015.
PMCID:8419947
PMID: 34488662
ISSN: 1471-2407
CID: 5011382
Impaired Humoral Immunity to SARS-CoV-2 Vaccination in Non-Hodgkin Lymphoma and CLL Patients
Diefenbach, Catherine; Caro, Jessica; Koide, Akiko; Grossbard, Michael; Goldberg, Judith D; Raphael, Bruce; Hymes, Kenneth; Moskovits, Tibor; Kreditor, Maxim; Kaminetzky, David; Fleur-Lominy, Shella Saint; Choi, Jun; Thannickal, Sara A; Stapleford, Kenneth A; Koide, Shohei
Patients with hematologic malignancies are a high priority for SARS-CoV-2 vaccination, yet the benefit they will derive is uncertain. We investigated the humoral response to vaccination in 53 non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), or CLL patients. Peripheral blood was obtained 2 weeks after first vaccination and 6 weeks after second vaccination for antibody profiling using the multiplex bead-binding assay. Serum IgG, IgA, and IgM antibody levels to the spike specific receptor binding domain (RBD) were evaluated as a measure of response. Subsequently, antibody-positive serum were assayed for neutralization capacity against authentic SARS-CoV-2. Histology was 68% lymphoma and 32% CLL; groups were: patients receiving anti-CD20-based therapy (45%), monitored with disease (28%), receiving BTK inhibitors (19%), or chemotherapy (all HL) (8%). SARS-CoV-2 specific RBD IgG antibody response was decreased across all NHL and CLL groups: 25%, 73%, and 40%, respectively. Antibody IgG titers were significantly reduced (p < 0.001) for CD20 treated and targeted therapy patients, and (p = 0.003) for monitored patients. In 94% of patients evaluated after first and second vaccination, antibody titers did not significantly boost after second vaccination. Only 13% of CD20 treated and 13% of monitored patients generated neutralizing antibodies to SARS-CoV-2 with ICD50s 135 to 1767, and 445 and > 10240. This data has profound implications given the current guidance relaxing masking restrictions and for timing of vaccinations. Unless immunity is confirmed with laboratory testing, these patients should continue to mask, socially distance, and to avoid close contact with non-vaccinated individuals.
PMCID:8183024
PMID: 34100025
ISSN: n/a
CID: 4899722
Hispanic or Latin American Ancestry Is Associated with a Similar Genomic Profile and a Trend Toward Inferior Outcomes in Newly Diagnosed Multiple Myeloma As Compared to Non-Hispanic White Patients in the Multiple Myeloma Research Foundation (MMRF) CoMMpassstudy [Meeting Abstract]
Williams, Louis; Blaney, Patrick; Boyle, Eileen M.; Ghamlouch, Hussein; Wang, Yubao; Choi, Jinyoung; Bauer, Michael A.; Siegel, Ariel; Stoeckle, James; Razzo, Beatrice; Auclair, Daniel; Kaminetzky, David; Braunstein, Marc; Bruno, Benedetto; Arbini, Arnaldo A.; Walker, Brian A.; Davies, Faith E.; Morgan, Gareth J.
ISI:000835740100118
ISSN: 0006-4971
CID: 5389192
Unifying the Definition of High-Risk in Multiple Myeloma [Meeting Abstract]
Siegel, Ariel; Boyle, Eileen M.; Blaney, Patrick; Wang, Yubao; Ghamlouch, Hussein; Choi, Jinyoung; Caro, Jessica; Williams, Louis; Razzo, Beatrice; Arbini, Arnaldo A.; Braunstein, Marc; Kaminetzky, David; Auclair, Daniel; Pawlyn, Charlotte; Cairns, David; Jackson, Graham; Walker, Brian; Bruno, Benedetto; Morgan, Gareth J.; Davies, Faith E.
ISI:000736413903013
ISSN: 0006-4971
CID: 5389182
Multiomic Mapping of Copy Number and Structural Variation on Chromosome 1 (Chr1) Highlights Multiple Recurrent Disease Drivers [Meeting Abstract]
Blaney, Patrick; Boyle, Eileen M.; Wang, Yubao; Ghamlouch, Hussein; Choi, Jinyoung; Williams, Louis; James, Stoeckle; Siegel, Ariel; Razzo, Beatrice; Braunstein, Marc; Kaminetzky, David; Arbini, Arnaldo A.; Bruno, Benedetto; Corre, Jill; Montes, Lydia; Auclair, Daniel; Davies, Faith E.; Tsirigos, Aristotelis; Rustad, Even H.; Maura, Francesco; Landgren, Ola; Bauer, Michael A.; Walker, Brian; Morgan, Gareth
ISI:000736398803021
ISSN: 0006-4971
CID: 5389172
COVID-19 Infections and Clinical Outcomes in Patients with Multiple Myeloma in New York City: A Cohort Study from Five Academic Centers
Hultcrantz, Malin; Richter, Joshua; Rosenbaum, Cara A; Patel, Dhwani; Smith, Eric L; Korde, Neha; Lu, Sydney X; Mailankody, Sham; Shah, Urvi A; Lesokhin, Alexander M; Hassoun, Hani; Tan, Carlyn; Maura, Francesco; Derkach, Andriy; Diamond, Benjamin; Rossi, Adriana; Pearse, Roger N; Madduri, Deepu; Chari, Ajai; Kaminetzky, David; Braunstein, Marc J; Gordillo, Christian; Reshef, Ran; Taur, Ying; Davies, Faith E; Jagannath, Sundar; Niesvizky, Ruben; Lentzsch, Suzanne; Morgan, Gareth J; Landgren, Ola
UNLABELLED:= 42), OR = 0.9 (0.3-2.2). In this largest cohort to date of patients with multiple myeloma and COVID-19, we found the case fatality rate to be 29% among hospitalized patients and that race/ethnicity was the most significant risk factor for adverse outcome. SIGNIFICANCE:.
PMID: 34651141
ISSN: 2643-3249
CID: 5507662
Pulmonary Embolism at CT Pulmonary Angiography in Patients with COVID-19
Kaminetzky, Mark; Moore, William; Fansiwala, Kush; Babb, James S; Kaminetzky, David; Horwitz, Leora I; McGuinness, Georgeann; Knoll, Abraham; Ko, Jane P
Purpose/UNASSIGNED:To evaluate pulmonary embolism (PE) prevalence at CT pulmonary angiography in patients testing positive for coronavirus disease 2019 (COVID-19) and factors associated with PE severity. Materials and Methods/UNASSIGNED:value < .05 was considered significant. Results/UNASSIGNED:< .001). One additional patient with negative results at CT pulmonary angiography had deep venous thrombosis, thus resulting in 38.7% with PE or deep venous thrombosis, despite 40% receiving prophylactic anticoagulation. Other factors did not demonstrate significant PE association. Conclusion/UNASSIGNED:© RSNA, 2020.
PMCID:7336753
PMID: 33778610
ISSN: 2638-6135
CID: 4830512
COVID-19 infections and outcomes in patients with multiple myeloma in New York City: a cohort study from five academic centers
Hultcrantz, Malin; Richter, Joshua; Rosenbaum, Cara; Patel, Dhwani; Smith, Eric; Korde, Neha; Lu, Sydney; Mailankody, Sham; Shah, Urvi; Lesokhin, Alexander; Hassoun, Hani; Tan, Carlyn; Maura, Francesco; Derkach, Andriy; Diamond, Benjamin; Rossi, Adriana; Pearse, Roger N; Madduri, Deppu; Chari, Ajai; Kaminetzky, David; Braunstein, Marc; Gordillo, Christian; Davies, Faith; Jagannath, Sundar; Niesvizky, Ruben; Lentzsch, Suzanne; Morgan, Gareth; Landgren, Ola
IMPORTANCE/OBJECTIVE:New York City is a global epicenter for the SARS-CoV-2 outbreak with a significant number of individuals infected by the virus. Patients with multiple myeloma have a compromised immune system, due to both the disease and anti-myeloma therapies, and may therefore be particularly susceptible to coronavirus disease 2019 (COVID-19); however, there is limited information to guide clinical management. OBJECTIVE:To assess risk factors and outcomes of COVID-19 in patients with multiple myeloma. DESIGN/METHODS:Case-series. SETTING/METHODS:Five large academic centers in New York City. PARTICIPANTS/METHODS:Patients with multiple myeloma and related plasma cell disorders who were diagnosed with COVID-19 between March 10th, 2020 and April 30th, 2020. Exposures: Clinical features and risk factors were analyzed in relation to severity of COVID-19. Main Outcomes and Measures: Descriptive statistics as well as logistic regression were used to estimate disease severity reflected in hospital admissions, intensive care unit (ICU) admission, need for mechanical ventilation, or death. RESULTS:Of 100 multiple myeloma patients (male 58%; median age 68, range 41-91) diagnosed with COVID-19, 74 (74%) were admitted; of these 13 (18%) patients were placed on mechanical ventilation, and 18 patients (24%) expired. None of the studied risk factors were significantly associated (P>0.05) with adverse outcomes (ICU-admission, mechanical ventilation, or death): hypertension (N=56) odds ratio (OR) 2.3 (95% confidence interval [CI] 0.9-5.9); diabetes (N=18) OR 1.1 (95% CI 0.3-3.2); age >65 years (N=63) OR 2.0 (95% CI 0.8-5.3); high dose melphalan with autologous stem cell transplant <12 months (N=7) OR 1.2 (95% CI 0.2-7.4), IgG<650 mg/dL (N=42) OR=1.2 (95% CI 0.4-3.1). In the entire series of 127 patients with plasma cell disorders, hypertension was significantly associated with the combined end-point (OR 3.4, 95% CI 1.5-8.1). CONCLUSIONS AND RELEVANCE/CONCLUSIONS:Although multiple myeloma patients have a compromised immune system due to both the disease and therapy; in this largest disease specific cohort to date of patients with multiple myeloma and COVID-19, compared to the general population, we found risk factors for adverse outcome to be shared and mortality rates to be within the higher range of officially reported mortality rates.
PMCID:7302217
PMID: 32577667
ISSN: n/a
CID: 4493182
Influence of Aging Processes on the Biology and Outcome of Multiple Myeloma [Meeting Abstract]
Boyle, Eileen M.; Williams, Louis; Blaney, Patrick; Ashby, Cody; Bauer, Michael A.; Walker, Brian A.; Choi, Jinyoung; Caro, Jessica; Razzo, Beatrice; Arbini, Arnaldo A.; Kaminetzky, David; Braunstein, Marc; Maura, Francesco; Wang, Yubao; Landgren, Ola; Stoeckle, James; Maclachlan, Kylee H.; Litke, Rachel; Davies, Faith E.; Morgan, Gareth
ISI:000607547201239
ISSN: 0006-4971
CID: 5389132
Oral Selinexor-Dexamethasone for Triple-Class Refractory Multiple Myeloma
Chari, Ajai; Vogl, Dan T; Gavriatopoulou, Maria; Nooka, Ajay K; Yee, Andrew J; Huff, Carol A; Moreau, Philippe; Dingli, David; Cole, Craig; Lonial, Sagar; Dimopoulos, Meletios; Stewart, A Keith; Richter, Joshua; Vij, Ravi; Tuchman, Sascha; Raab, Marc S; Weisel, Katja C; Delforge, Michel; Cornell, Robert F; Kaminetzky, David; Hoffman, James E; Costa, Luciano J; Parker, Terri L; Levy, Moshe; Schreder, Martin; Meuleman, Nathalie; Frenzel, Laurent; Mohty, Mohamad; Choquet, Sylvain; Schiller, Gary; Comenzo, Raymond L; Engelhardt, Monika; Illmer, Thomas; Vlummens, Philip; Doyen, Chantal; Facon, Thierry; Karlin, Lionel; Perrot, Aurore; Podar, Klaus; Kauffman, Michael G; Shacham, Sharon; Li, Lingling; Tang, Shijie; Picklesimer, Carla; Saint-Martin, Jean-Richard; Crochiere, Marsha; Chang, Hua; Parekh, Samir; Landesman, Yosef; Shah, Jatin; Richardson, Paul G; Jagannath, Sundar
BACKGROUND:Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options. METHODS:We administered oral selinexor (80 mg) plus dexamethasone (20 mg) twice weekly to patients with myeloma who had previous exposure to bortezomib, carfilzomib, lenalidomide, pomalidomide, daratumumab, and an alkylating agent and had disease refractory to at least one proteasome inhibitor, one immunomodulatory agent, and daratumumab (triple-class refractory). The primary end point was overall response, defined as a partial response or better, with response assessed by an independent review committee. Clinical benefit, defined as a minimal response or better, was a secondary end point. RESULTS:A total of 122 patients in the United States and Europe were included in the modified intention-to-treat population (primary analysis), and 123 were included in the safety population. The median age was 65 years, and the median number of previous regimens was 7; a total of 53% of the patients had high-risk cytogenetic abnormalities. A partial response or better was observed in 26% of patients (95% confidence interval, 19 to 35), including two stringent complete responses; 39% of patients had a minimal response or better. The median duration of response was 4.4 months, median progression-free survival was 3.7 months, and median overall survival was 8.6 months. Fatigue, nausea, and decreased appetite were common and were typically grade 1 or 2 (grade 3 events were noted in up to 25% of patients, and no grade 4 events were reported). Thrombocytopenia occurred in 73% of the patients (grade 3 in 25% and grade 4 in 33%). Thrombocytopenia led to bleeding events of grade 3 or higher in 6 patients. CONCLUSIONS:Selinexor-dexamethasone resulted in objective treatment responses in patients with myeloma refractory to currently available therapies. (Funded by Karyopharm Therapeutics; STORM ClinicalTrials.gov number, NCT02336815.).
PMID: 31433920
ISSN: 1533-4406
CID: 4046822