Open Innovation within Life Sciences: Industry-Specific Challenges and How to Improve Interaction with External Ecosystems

While Open Innovation (OI) and user integration have been applied across industries over the last two decades more professionally and digitally, the life science (LS) sector has various obstacles and regulations to overcome in order to implement and execute OI initiatives as well as entire programs. Moreover, scientific research has been scarce on analyzing data in this industry. The number of companies applying OI methodologies has risen significantly in the last couple of years. However, intellectual property (IP) and data protection make it hard to get access to good insights. However, we have accompanied ten LS companies (including 48 OI initiatives/programs) using an action research approach based on various data (e.g., interviews) over ten years, including the time of the outbreak and dissemination of the COVID-19 pandemic. In this paper, we will share insights about 1) the unique characteristics of OI in the LS sector compared to other industries, 2) the identification of used OI methodologies and their success criteria, as well as 3) the change and influence of the COVID-19 pandemic on the use of OI programs in the LS sector. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.

Managing hematological cancer patients during the COVID-19 pandemic: an ESMO-EHA Interdisciplinary Expert Consensus.

BACKGROUND: The COVID-19 pandemic has created enormous challenges for the clinical management of patients with hematological malignancies (HMs), raising questions about the optimal care of this patient group. METHODS: This consensus manuscript aims at discussing clinical evidence and providing expert advice on statements related to the management of HMs in the COVID-19 pandemic. For this purpose, an international consortium was established including a steering committee, which prepared six working packages addressing significant clinical questions from the COVID-19 diagnosis, treatment, and mitigation strategies to specific HMs management in the pandemic. During a virtual consensus meeting, including global experts and lead by the European Society for Medical Oncology and the European Hematology Association, statements were discussed and voted upon. When a consensus could not be reached, the panel revised statements to develop consensual clinical guidance. RESULTS AND CONCLUSION: The expert panel agreed on 33 statements, reflecting a consensus, which will guide clinical decision making for patients with hematological neoplasms during the COVID-19 pandemic.

Mobilization and collection of hematopoietic stem cells in poorly mobilizable patients with multiple myeloma and lymphoma across Germany: Interim analysis of the OPTIMOB study

Autologous stem cell transplantation (ASCT) is an effective procedure for the treatment of multiple myeloma (MM) and lymphoma patients, but an adequate hematopoietic stem cell (HSC) yield is essential. In some patients (poor mobilizers, PM), stem cell mobilization is difficult leading to repeated apheresis sessions and increased patients' burden. Plerixafor (PLX), in combination with granulocyte colony stimulating factor (G-CSF) has been shown to effectively mobilize HSCs in PM patients. The OPTIMOB study is a prospective, multi-center, non-interventional, observational study to evaluate the current approach of HSC mobilization and collection regimen as well as ASCT procedures in German MM and lymphoma patients with special focus on PM patients. It is expected to enroll at least 210 poor mobilizers in this study. This prespecified interim analysis was performed after the complete documentation of the first 100 poor mobilizers. Until data cut-off in November 2020, 461 patients from 28 sites were enrolled. 66% of the patients suffered from MM, 63% were male and mean age was 59 years (SD: ±9.55). In total, 38% of the patients were classified as PM. PLX was used in 83% of the PM patients during mobilization, mainly due to low CD34+ cell content in peripheral blood (72% of the patients). Collection target was reached in 72% of patients receiving PLX versus 50% of PM who did not receive PLX. In total, 87% of PM patients underwent apheresis. Mean collection result of the first day of apheresis was 7.2 cells x106/kg bw (SD: ± 28.13) in PM patients with PLX versus 3.7 cells x106/ kg bw [SD: ±3.44]) in PM patients without PLX. ASCT was performed in 67% of the PM patients at the data cut-off. Adverse events occurred in 39% of the study population but were not related to PLX use. Mean number of induction cycles and apheresis days as well as the elapsed time between start of mobilization and transplantation did not seem to change in the study population during the SARS-CoV-2 pandemic. However, there was a tendency towards more frequently use of G-SCF for mobilization instead of chemotherapeutic based mobilization regimes. In Germany, a high number of MM and lymphoma patients appear to be PMs. This interim analysis of the OPTIMOB study shows that adding PLX to standardized mobilization strategies is associated with an adequate mobilization of CD34+ cells in 3 out of 4 PMs, allowing them to undergo ASCT.

Poor Outcome of Patients with COVID-19 after CAR T-Cell Therapy for B-Cell Malignancies: Results from a Multicenter Study on Behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Background The ongoing Coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is having an enormous impact on society worldwide and is especially posing a threat to health in vulnerable patients, such as patients with immune deficiencies. It is expected that patients who received Chimeric Antigen Receptor T-cell (CAR T-cell) therapy for hematologic malignancies are at risk for poor outcomes after COVID-19 due to their severely immunocompromised state caused by prior cumulative immunochemotherapy, on-target/off-tumor B-cell depletion, hypogammaglobulinemia and ongoing cytopenias. Current data are limited to small case series and case reports. This study describes the clinical characteristics and outcomes of CAR T-cell therapy recipients after developing COVID-19 in the largest cohort to date. Methods In response to the COVID-19 pandemic, the European Society for Blood and Marrow Transplantation (EBMT) developed a special COVID-19 report form to capture data from all patients with COVID-19 after treatment with CAR T-cell therapy for hematologic malignancies. Only PCR positive SARS-CoV-2 diagnosed patients before June 1 st, 2021 were included. The aim of this study was to describe the clinical course after COVID-19 diagnosis and evaluate overall survival. Overall survival probabilities were calculated using the Kaplan Meier method. Factors associated with mortality after COVID-19 diagnosis were examined using a Cox proportional hazard model. Results A total of 57 patients from 11 countries were reported to the EBMT. One patient with incomplete data at diagnosis and without any follow up information had to be excluded from the analysis. The median age of these 56 patients was 57.7 years (min-max 5.2 - 72.8) including 55 adults and one child. Of these patients, 32 were male. CAR T-cell therapy was given to 46 patients with B-cell-non-Hodgkin lymphoma, 7 patients with B-cell acute lymphoblastic leukemia, and 3 patients with multiple myeloma. The median time from CAR T-cell infusion to COVID-19 diagnosis was 7.4 months (min-max 0.03 - 25.3). At the time of COVID-19 diagnosis, 62.5% of patients were in complete remission, 12.5% of patients had a partial response and 25% of patients had relapsed/refractory disease. Forty-five patients (80%) were admitted to hospital (median 26,5 days, min-max 3-171) due to COVID-19. Of the admitted patients, 24 (53%) needed oxygen support. Twenty-two (49%) patients were admitted to the intensive care unit (median 14 days, min - max 2-65) and 16 (73%) of these patients received invasive ventilation. At the time of analysis, 25 of the 56 patients had died (44.6%), most (23/25) due to COVID-19, resulting in a COVID-19 attributable mortality rate of 41%. The Kaplan-Meier estimate of overall survival is shown in Figure 1. The median follow-up from COVID-19 diagnosis was 20.9 weeks. In 1 of the 32 alive patients there was no resolution of COVID-19 at the time of analysis. In multivariate analysis, older age (hazard ratio (HR) 1.50, 95% CI 1.11-2.03, p=0.009) and comorbidities (HR 2.56, 95% CI 1.05-6.23, p=0.001) had a negative impact on overall survival. Better performance status at time of admission (HR 0.72, 95% CI 0.59-0.88, p=0.038) had a positive impact on overall survival. Sex, time from CAR T-cell therapy to COVID-19 diagnosis, disease remission status and the occurrence of neurotoxicity or cytokine release syndrome after CAR T-cell infusion did not have a significant effect on overall survival in the multivariate analysis. Conclusion Patients with COVID-19 after B-cell-targeted CAR T-cell therapy have a very poor outcome. As it remains uncertain whether currently applied vaccination strategies against SARS-CoV-2 are effective after CAR T-cell therapy, vaccination of health-care personnel and family members in combination with protective measures against viral exposure are likely to play the most important role in protecting this vulnerable group of patients. Better treatment strategies are urgently needed. [Formula present d] Disclosures: Ljungman: OctaPharma: Other: DSMB;Enanta: Other: DSMB;Janssen: Other: Investigator;Takeda: Consultancy, Other: Endpoint committee, speaker;AiCuris: Consultancy;Merck: Other: Investigator, speaker. De La Camara: IQONE: Consultancy;Roche: Consultancy. Ortiz-Maldonado: Kite, Novartis, BMS, Janssen: Honoraria. Barba: Novartis: Honoraria;Gilead: Honoraria;BMS: Honoraria;Amgen: Honoraria;Pfizer: Honoraria. Kwon: Novartis, Celgene, Gilead, Pfizer: Consultancy, Honoraria. Sesques: Novartis: Honoraria;Chugai: Honoraria;Kite, a Gilead Company: Honoraria. Bachy: Kite, a Gilead Company: Honoraria;Novartis: Honoraria;Daiishi: Research Funding;Roche: Consultancy;Takeda: Consultancy;Incyte: Consultancy. Di Blasi: Kite, a Gilead Company: Consultancy, Honoraria;Novartis: Consultancy, Honoraria;Janssen: Consultancy, Honoraria. Thieblemont: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees;Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees;Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses, Research Funding;Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees;Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses;Hospira: Research Funding;Bayer: Honoraria;Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses. Mutsaers: BMS: Consultancy;AstraZeneca: Research Funding. Nicholson: Kite, a Gilead Company: Other: Conference fees, Speakers Bureau;Novartis: Consultancy, Other: Conference fees;BMS/Celgene: Consultancy;Pfizer: Consultancy. Martínez-López: Janssen, BMS, Novartis, Incyte, Roche, GSK, Pfizer: Consultancy;Roche, Novartis, Incyte, Astellas, BMS: Research Funding. Ribera: NOVARTIS: Consultancy, Speakers Bureau;TAKEDA: Consultancy, Research Funding, Speakers Bureau;ARIAD: Consultancy, Research Funding, Speakers Bureau;SHIRE: Consultancy, Speakers Bureau;AMGEN: Consultancy, Research Funding, Speakers Bureau;Pfizer: Consultancy, Research Funding, Speakers Bureau. Sanderson: Kite, a Gilead Company: Honoraria;Novartis: Honoraria. Bloor: Kite, a Gilead Company: Honoraria;Novartis: Honoraria. Ciceri: IRCCS Ospedale San Raffaele: Current Employment. Ayuk: Novartis: Honoraria;Janssen: Honoraria;Takeda: Honoraria;Mallinckrodt/Therakos: Honoraria, Research Funding;Gilead: Honoraria;Miltenyi Biomedicine: Honoraria;Celgene/BMS: Honoraria. Kröger: Novartis: Research Funding;Riemser: Honoraria, Research Funding;Sanofi: Honoraria;Neovii: Honoraria, Research Funding;Jazz: Honoraria, Research Funding;Gilead/Kite: Honoraria;Celgene: Honoraria, Research Funding;AOP Pharma: Honoraria. Kersten: Celgene: Research Funding;Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support;Roche: Consultancy, Honoraria, Other: Travel support, Research Funding;BMS/Celgene: Consultancy, Honoraria;Takeda: Research Funding;Novartis: Consultancy, Honoraria, Other: Travel support;Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding. Mielke: DNA Prime SA: Speakers Bureau;Im unicum: Other: Data safety monitoring board;Novartis: Speakers Bureau;Miltenyi: Other: Data safety monitoring board;Gilead/KITE: Other: Travel support, Expert panel;Celgene/BMS: Speakers Bureau.