Autologous haematopoietic stem-cell transplantation versus bortezomib–melphalan–prednisone, with or without bortezomib–lenalidomide–dexamethasone consolidation therapy, and lenalidomide maintenance for newly diagnosed multiple myeloma (EMN02/HO95): a multicentre, randomised, open-label, phase 3 study

Cavo, Michèle; Gay, Francesca; Beksaç, Meral; Pantani, Lucia; Petrucci, Maria Teresa; Dimopoulos, Meletios A.; Dozza, Luca; Holt, Bronno van der; Zweegman, Sonja; Oliva, Stefania; Velden, Vincent H.J. van der; Zamagni, Elena; Palumbo, Giuseppe A.; Patriarca, Francesca; Montefusco, Vittorio; Galli, Mónica; Maisnar, Vladimír; Gamberi, Barbara; Hansson, Markus; Belotti, Angelo; Pour, Luděk; Ypma, Paula F.; Grasso, Mariella; Croockewit, Alexandra J.; Ballanti, Stelvio; Offidani, Massimo; Vincelli, Iolanda Donatella; Zambello, Renato; Liberati, Anna Marina; Andersen, Niels Frost; Broijl, Annemiek; Troia, Rossella; Pascarella, Anna; Benevolo, Giulia; Levin, Mark‐David; Bos, Gerard M.J.; Ludwig, Heinz; Aquino, Sara; Morelli, Anna; Wu, Ka Lung; Boersma, Rinske; Hájek, Roman; Durian, Marc; Borne, Peter A. von dem; Toritto, Tommaso Caravita di; Zander, Thilo; Driessen, Christoph; Specchia, Giorgina; Waage, Anders; Gimsing, Peter; Mellqvist, Ulf‐Henrik; Kooy, Marinus van Marwijk; Minnema, Monique C.; Mandigers, Caroline; Cafro, Anna Maria; Palmas, Angelo; Carvalho, Susanna; Spencer, Andrew; Boccadoro, Mario; Sonneveld, Pieter

doi:10.1016/s2352-3026(20)30099-5

Cited by 273 publications

(258 citation statements)

References 28 publications

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“…Independent of COVID-19, typically, patients with multiple myeloma are at an increased risk of infections due to both disease-and treatment-associated immunosuppression (15,23). Examples of these associations are the immunomodulatory and conventional chemotherapy drugs, which cause myelosuppression, and the targeted mAbs such as anti-CD38 associated with suppression of the humoral immune system (24)(25)(26)(27)(28). In this series, we did not identify an association between anti-myeloma treatment or hypogammaglobulinemia and adverse outcome; however, due to the lack of detailed biomarker data, we were unable to rule out associations involving other immunologic mechanisms (such as T-cell suppression) that are important in the immune response toward viral and other infections.…”

Section: Discussionmentioning

confidence: 99%

COVID-19 Infections and Clinical Outcomes in Patients with Multiple Myeloma in New York City: A Cohort Study from Five Academic Centers

Hultcrantz

Richter

Rosenbaum

et al. 2020

Blood Cancer Discovery

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Patients with multiple myeloma have a compromised immune system, due to both the disease and antimyeloma therapies, and may therefore be particularly susceptible to COVID-19. Here, we report outcomes and risk factors for serious disease in patients with multiple myeloma treated at five large academic centers in New York City in the spring of 2020, during which it was a global epicenter of the SARS-CoV-2 pandemic. Of 100 patients with multiple myeloma (male 58%; median age 68) diagnosed with COVID-19, 75 were admitted; of these, 13 patients (17%) were placed on invasive mechanical ventilation, and 22 patients (29%) expired. Of the 25 nonadmitted patients, 4 were asymptomatic. There was a higher risk of adverse outcome (intensive care unit admission, mechanical ventilation, or death) in Hispanics/Latinos (n = 21), OR = 4.7 (95% confidence interval, 1.3-16.7), and African American Blacks (n = 33), OR = 3.5 (1.1-11.5), as compared with White patients (n = 36). Patients who met the adverse combined endpoint had overall higher levels of inflammatory markers and cytokine activation. None of the other studied risk factors were significantly associated (P > 0.05) with adverse outcome: hypertension (n = 56), OR = 2.2 (0.9-5.4); diabetes (n = 18), OR = 0.9 (0.3-2.9); age >65 years (n = 63), OR = 1.8 (0.7-4.6); high-dose melphalan with autologous stem cell transplant <12 months (n = 7), OR = 0.9 (0.2-5.4); and immunoglobulin G <650 mg/dL (n = 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: Patients with multiple myeloma are immunocompromised, raising the question whether they are at higher risk of severe COVID-19 disease. In this large case series on COVID-19 in patients with multiple myeloma, we report 29% mortality rates among hospitalized patients and identify race/ ethnicity as the most significant risk factor for severe outcome.

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Section: Discussionmentioning

confidence: 99%

COVID-19 Infections and Clinical Outcomes in Patients with Multiple Myeloma in New York City: A Cohort Study from Five Academic Centers

Hultcrantz

Richter

Rosenbaum

et al. 2020

Blood Cancer Discovery

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“…However, a meta-analysis of LenMT trials revealed for patients with lenalidomide induction a better OS as compared with those without (10). Actually, the lacking lenalidomide induction in our study might have been outweighed by the consolidation therapy: one phase III trial with lenalidomide-based induction did not observe any benefit from subsequent consolidation with bortezomib, lenalidomide, and dexamethasone (12), while another phase III trial not using lenalidomide for induction did show a significant PFS benefit from lenalidomide-containing consolidation therapy (18). Notably, the difference in PFS between arms in our study was persistent, regardless of whether the analysis referred to the start of LenCT (Fig.…”

Section: Limitations Of Study Designmentioning

confidence: 52%

Efficacy and Tolerability of High- versus Low-dose Lenalidomide Maintenance Therapy of Multiple Myeloma after Autologous Blood Stem Cell Transplantation

Fenk

Giagounidis

Goldschmidt

et al. 2020

Clinical Cancer Research

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For multiple myeloma, high-dose chemotherapy and autologous blood stem-cell transplantation (ASCT) followed by lenalidomide maintenance (LenMT) at 10-15 mg/day is considered standard of care. However, dose reductions due to side effects are common and median LenMT doses achieved over time may remain lower. Dose response during LenMT has never been investigated. Patients and Methods: In a multicenter, randomized, open-label trial, patients with multiple myeloma after ASCT and high-dose lenalidomide consolidation therapy (CT) at 25 mg/day were randomized to receive LenMT at either 25 or 5 mg/day. Primary endpoint was progression-free survival (PFS). Results: Ninety-four patients (median age, 58 years) were randomized to either arm, with 22% having International Staging System (ISS) stage 3 and 22% being in complete remission (CR). After median follow-up of 46.7 months, median doses of 14.5 and 5 mg/day were achieved in the two arms; 53% of dose reductions occurring during CT. In the high-and the low-dose arm, median PFS was 44.8 and 33.0 months (HR, 0.65; 95% CI, 0.44-0.97; P ¼ 0.032), 36% and 23% of patients had stringent CR as best response (P ¼ 0.08), and 4-year OS was 79% and 67% (P ¼ 0.16), respectively. Hematologic toxicity, grade ≥3 neutropenia, and infections were initially more common with LenMT 25 mg, but decreased after dose adjustments. SPM incidence and quality-oflife (QoL) scores in both arms were similar. Conclusions: LenMT dose correlated with efficacy and toxicity. High rates of dose reductions during CT argue against a high starting dose. However, continuous up-and down-titration for each patient to the current maximum tolerated dose is prudent.

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“…High dose melphalan followed by ASCT is the treatment of choice for younger patients with newly diagnosed MM who are eligible for such a procedure (33). However, balancing the risks of COVID-19 infection and MM-related mortality is difficult and, therefore, in the current setting of the COVID-19 pandemic, deciding whether ASCT has to be performed, delayed, or excluded should be carefully evaluated on a case by case basis.…”

Section: Newly Diagnosed Patients Eligible For Asctmentioning

confidence: 99%

Management of Patients With Hematologic Malignancies During the COVID-19 Pandemic: Practical Considerations and Lessons to Be Learned

Isidori¹,

Leval

Gergis

et al. 2020

Front. Oncol.

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The COVID-19 pandemic has created unprecedented hurdles to the delivery of care to patients with cancer. Patients with hematologic malignancies appear to have a greater risk of SARS-CoV-2 infection and severe disease due to myelosuppression and lymphopenia. The first challenge, therefore, is how to continue to deliver effective, curative therapy to vulnerable patients and at the same time avoid exposing them, and their health care teams (HCT), to SARS-CoV-2. An additional challenge is the timely completion of the diagnostic and staging studies required to formulate appropriate treatment plans. Deferred procedures and avoidance of multiple trips to the surgical, diagnostic, and laboratory suites require same day consolidation of all procedures. With laboratory medicine absorbed by the need to deploy large scale COVID-testing, the availability of routine molecular tests is affected. Finally, we are increasingly faced with the challenge of making complex treatment decisions in SARS-CoV-2 positive patients with aggressive but potentially curable blood cancers. When to treat, how to treat, when to wait, how long to wait, how to predict and manage toxicities, and how to avoid compromising cure rates remains unknown. We present an outline of the scientific, medical, and operational challenges posed by the COVID-19 pandemic at selected American and European institutions and offer our current view of the key elements of a response. While the peak of the pandemic may be past us, in the absence of a vaccine risks remain, and our alertness and response to future challenges need to be refined and consolidated.

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Cited by 273 publications

References 28 publications

COVID-19 Infections and Clinical Outcomes in Patients with Multiple Myeloma in New York City: A Cohort Study from Five Academic Centers

COVID-19 Infections and Clinical Outcomes in Patients with Multiple Myeloma in New York City: A Cohort Study from Five Academic Centers

Efficacy and Tolerability of High- versus Low-dose Lenalidomide Maintenance Therapy of Multiple Myeloma after Autologous Blood Stem Cell Transplantation

Management of Patients With Hematologic Malignancies During the COVID-19 Pandemic: Practical Considerations and Lessons to Be Learned

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