Effectiveness of fractionated rituximab in preventing tumor lysis syndrome in aggressive B-cell lymphoma: Insights from real-life clinical practice.

BACKGROUND: Tumor lysis syndrome (TLS) is a potentially life-threatening condition resulting from the rapid destruction of malignant cells, leading to electrolyte imbalances and severe complications, such as acute kidney injury, arrhythmias, and seizures. TLS can be managed through hyperhydration, urate-lowering treatments, and a steroid prophase strategy. AIMS: This study aims to explore the impact of fractionated rituximab, an anti-CD20 antibody, on the occurrence and severity of TLS during the initial cycle in patients with aggressive B-cell non-Hodgkin lymphoma (B-NHL). METHODS: Data was retrospectively collected from 94 of 186 patients. RESULTS: Among the 94 patients included in the analysis, the median age was 70. Histologies were diffuse large B-cell lymphoma (75%), Burkitt lymphoma (13%) and high-grade B-cell lymphoma (8%). The majority were at an advanced stage (93%) with a high IPI score (75%). Most patients received anthracycline-containing regimens (72%) and prophylactic allopurinol (83%) and/or rasburicase (26%). Steroid prophase was administered to 82% of patients. The study identified one clinical TLS case and six laboratory TLS cases. Significant TLS factors included BL histology, elevated baseline LDH (⟩500 U/l), and rasburicase usage. Infusion reactions were rare (3%). Median progression-free survival was 2.6 years, and 2-year overall survival was 33%, irrespective of TLS occurrence. CONCLUSION: In this real-life study, clinical TLS occurrence was low (1%). TLS appeared more frequent in BL but did not impact overall survival. Fractionated initial rituximab dosing in addition to preventive strategies is a feasible approach in preventing clinical TLS, warranting further prospective investigation.

Sabatolimab in combination with spartalizumab in patients with non-small cell lung cancer or melanoma who received prior treatment with anti-PD-1/PD-L1 therapy: a phase 2 multicentre study.

OBJECTIVE: This study evaluates the safety/efficacy of sabatolimab plus spartalizumab in patients with melanoma or non-small cell lung cancer (NSCLC). DESIGN, SETTING AND PARTICIPANTS: This is a phase 1-1b/2, open-label, multinational, multicentre study of patients with advanced/metastatic melanoma or NSCLC with ≥1 measurable lesion. INTERVENTIONS: Patients were given sabatolimab 800 mg every 4 weeks plus spartalizumab 400 mg every 4 weeks until unacceptable toxicity, disease progression and/or treatment discontinuation. OUTCOME MEASURES: The phase 2 primary outcome measure was overall response rate and secondary objectives included evaluation of the safety, tolerability, efficacy and pharmacokinetics of sabatolimab in combination with spartalizumab. RESULTS: 33 patients (melanoma n=16, NSCLC n=17) received sabatolimab plus spartalizumab. 31 (94%) experienced ≥1 adverse event (AE); 15 (46%) experienced grade 3/4 events. The most frequent grade ≥3 AEs for NSCLC were anaemia, dyspnoea and pneumonia (each n=2, 12%); for patients with melanoma, the most frequent grade ≥3 AEs were physical health deterioration, hypokalaemia, hypophosphataemia, pathological fracture and tumour invasion (each n=1; 6%). One (3%) patient discontinued treatment due to AE. Stable disease was seen in three patients with melanoma (19%) and six patients with NSCLC (35%). Median progression-free survival was 1.8 (90% CI 1.7 to 1.9) and 1.7 (90% CI 1.1 to 3.4) months for patients with melanoma and NSCLC, respectively. Patients with stable disease had higher expression levels of CD8, LAG3, programmed death-ligand 1 and anti-T-cell immunoglobulin and mucin-domain containing-3 at baseline. The pharmacokinetics profile of sabatolimab was consistent with the phase 1 study. CONCLUSIONS: Sabatolimab plus spartalizumab was well tolerated in patients with advanced/metastatic melanoma or NSCLC who had progressed following antiprogrammed death-1/antiprogrammed death-ligand 1 treatment. Limited antitumour activity was observed. The tolerability of sabatolimab administration supports the potential to explore treatment with sabatolimab in various combination regimens and across a spectrum of tumour types. TRIAL REGISTRATION NUMBER: NCT02608268.

A First-in-Human Phase I Clinical Study with MVX-ONCO-1, a Personalized Active Immunotherapy, in Patients with Advanced Solid Tumors.

Over two decades, most cancer vaccines failed clinical development. Key factors may be the lack of efficient priming with tumor-specific antigens and strong immunostimulatory signals. MVX-ONCO-1, a personalized cell-based cancer immunotherapy, addresses these critical steps utilizing clinical-grade material to replicate a successful combination seen in experimental models: inactivated patient's own tumor cells, providing the widest cancer-specific antigen repertoire and a standardized, sustained, local delivery over days of a potent adjuvant achieved by encapsulated cell technology. We conducted an open-label, single-arm, first-in-human phase I study with MVX-ONCO-1 in patients with advanced refractory solid cancer. MVX-ONCO-1 comprises irradiated autologous tumor cells coimplanted with two macrocapsules containing genetically engineered cells producing granulocyte-macrophage colony-stimulating factor. Patients received six immunizations over 9 weeks without maintenance therapy. Primary objectives were safety, tolerability, and feasibility, whereas secondary objectives focused on efficacy and immune monitoring. Data from 34 patients demonstrated safety and feasibility with minor issues. Adverse events included one serious adverse event possibly related to investigational medicinal product and two moderate-related adverse events. More than 50% of the patients with advanced and mainly nonimmunogenic tumors showed clinical benefits, including partial responses, stable diseases, and prolonged survival. In recurrent/metastatic head and neck squamous cell carcinoma, one patient achieved a partial response, whereas another survived for more than 7 years without anticancer therapy for over 5 years. MVX-ONCO-1 is safe, well tolerated, and beneficial across several tumor types. Ongoing phase IIa trials target patients with advanced recurrent/metastatic head and neck squamous cell carcinoma after initial systemic therapy. SIGNIFICANCE: This first-in-human phase I study introduces a groundbreaking approach to personalized cancer immunotherapy, addressing limitations of traditional strategies. By combining autologous irradiated tumor cells as a source of patient-specific antigens and utilizing encapsulated cell technology for localized, sustained delivery of granulocyte-macrophage colony-stimulating factor as an adjuvant, the study shows a very good safety and feasibility profile. This innovative approach holds the promise of addressing tumor heterogeneity by taking advantage of each patient's antigenic repertoire.

ONE SHOT - single shot radiotherapy for localized prostate cancer: 18-month results of a single arm, multicenter phase I/II trial.

PURPOSE: To assess in a prospective, multicenter, single-arm phase I/II study the early safety and efficacy profile of single fraction urethra-sparing stereotactic body radiotherapy (SBRT) for men with localized prostate cancer. MATERIAL AND METHODS: Patients with low- and intermediate-risk localized prostate cancer without significant tumor in the transitional zone were recruited. A single-fraction of 19 Gy was delivered to the prostate, with 17 Gy dose-reduction to the urethra. Intrafraction motion was monitored using intraprostatic electromagnetic transponders with intra-fraction correction of displacements exceeding 3 mm. Genitourinary (GU), gastrointestinal (GI), and sexual toxicity during the first 18 months were evaluated using the CTCAE v4.0 grading scale. Quality of life was assessed using the International Prostate Symptom Score, the Expanded Prostate Cancer Index composite 26 score, and the International Index of Erectile Function score. RESULTS: Among the 45 patients recruited in 5 centers between 2017 and 2022, 43 received the single fraction without protocol deviations, and 34 had a minimal follow-up of 18 months. The worst GU toxicity was observed at day-5 after SBRT (42.5 % and 20 % with grade 1 and 2, respectively), returning to baseline at week-12 and month-6 (<3% with grade 2), with a 12 % grade 2 flare at month 18. Gl toxicity was mild in the acute phase, with no grade ≥ 2 events (12 % grade 1 at month 6). Grade-3 proctitis was observed in one patient at month 12, with < 3 % grade 2 toxicity at month 18. Mean GU and GI bother scores showed a decline at day 5, a complete recovery at month 6, and a flare between month 12 and 18. Mean PSA dropped from 6.2 ng/ml to 1.2 ng/ml at month 18 and 0.7 ng/ml at month 24. After a median follow-up time of 26 months, 3 biochemical failures (7 %) were observed at month 17, 21 and 30. CONCLUSIONS: In this multicenter phase I/II trial, we demonstrated that a 19 Gy single-fraction urethra-sparing SBRT is feasible and associated with an acceptable toxicity rate, mostly returning to the baseline at week-12 and with a symptoms flare between months 12 and 18. Longer follow-up is needed to assess the potential long-term adverse effects and the disease control efficacy.

PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM): Acute Toxicity of a Randomized Phase 2 Trial.

BACKGROUND: Treatment recommendations for patients with limited nodal recurrences are lacking, and different locoregional treatment approaches are currently being used. OBJECTIVE: The aim of this trial is to compare metastasis-directed therapy (MDT) with or without elective nodal pelvic radiotherapy (ENRT). DESIGN, SETTING, AND PARTICIPANTS: PEACE V-Salvage Treatment of OligoRecurrent nodal prostate cancer Metastases (STORM) is an international, phase 2, open-label, randomized, superiority trial (ClinicalTrials.gov identifier: NCT03569241). Patients diagnosed with positron emission tomography-detected pelvic nodal oligorecurrence (five or fewer nodes) following radical local treatment for prostate cancer were randomized in a 1:1 ratio between arm A (MDT and 6 mo of androgen deprivation therapy [ADT]) and arm B (ENRT [25 × 1.8 Gy] with MDT and 6 mo of ADT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We report the secondary endpoint acute toxicity, defined as worst grade ≥2 Common Terminology Criteria for Adverse Events v4.0 gastrointestinal (GI) or genitourinary (GU) toxicity within 3 mo of treatment. The chi-square test was used to compare toxicity between treatment arms. We also compare the quality of life (QoL) using the European Organisation for Research and Treatment of Cancer QLQ C30 and PR25 questionnaires. RESULTS AND LIMITATIONS: Between June 2018 and April 2021, 196 patients were assigned randomly to MDT or ENRT. Ninety-seven of 99 patients allocated to MDT and 93 of 97 allocated to ENRT received per-protocol treatment. Worst acute GI toxicity proportions were as follows: grade ≥2 events in three (3%) in the MDT group versus four (4%) in the ENRT group (p = 0.11). Worst acute GU toxicity proportions were as follows: grade ≥2 events in eight (8%) in the MDT group versus 12 (13%) in the ENRT group (p = 0.95). We observed no significant difference between the study groups in the proportion of patients with a clinically significant QoL reduction from baseline for any subdomain score area. CONCLUSIONS: No clinically meaningful differences were observed in worst grade ≥2 acute GI or GU toxicity or in QoL subdomains between MDT and ENRT. PATIENT SUMMARY: We found no evidence of differential acute bowel or urinary side effects using metastasis-directed therapy and elective nodal radiotherapy for the treatment of patients with a pelvic lymph node recurrence.

Erratum: Immortalized human myoblast cell lines for the delivery of therapeutic proteins using encapsulated cell technology.

[This corrects the article DOI: 10.1016/j.omtm.2022.07.017.].

Combined therapy with ibrutinib and bortezomib followed by ibrutinib maintenance in relapsed or refractory mantle cell lymphoma and high-risk features: a phase 1/2 trial of the European MCL network (SAKK 36/13).

Background: The Bruton's tyrosine kinase inhibitor ibrutinib and the proteasome inhibitor bortezomib have single-agent activity, non-overlapping toxicities, and regulatory approval in mantle cell lymphoma (MCL). In vitro, their combination provides synergistic cytotoxicity. In this investigator-initiated phase 1/2 trial, we established the recommended phase 2 dose of ibrutinib in combination with bortezomib, and assessed its efficacy in patients with relapsed or refractory MCL. Methods: In this phase 1/2 study open in 15 sites in Switzerland, Germany and Italy, patients with relapsed or refractory MCL after ≤2 lines of chemotherapy and both ibrutinib-naïve and bortezomib-naïve received six cycles of ibrutinibb and bortezomib, followed by ibrutinib maintenance. For the phase 1 study, a standard 3 + 3 dose escalation design was used to determine the recommended phase 2 dose of ibrutinib in combination with bortezomib. The primary endpoint in phase 1 was the dose limiting toxicities in cycle 1. The phase 2 study was an open-label, single-arm trial with a Simon's two-stage min-max design, with a primary endpoint of overall response rate (ORR) assessed by CT/MRI. This study was registered with ClinicalTrials.gov, NCT02356458. Findings: Between August 2015 and September 2016, nine patients were treated in the phase 1 study, and 49 patients were treated between November 2016 and March 2020 in the phase 2 of the trial. The ORR was 81.8% (90% CI 71.1, 89.8%, CR(u) 21.8%) which increased with continued ibrutinib (median 10.6 months) to 87.3%, (CR(u) 41.8%). 75.6% of patients had at least one high-risk feature (Ki-67 > 30%, blastoid or pleomorphic variant, p53 overexpression, TP53 mutations and/or deletions). In these patients, ibrutinib and bortezomib were also effective with an ORR of 74%, increasing to 82% during maintenance. With a median follow-up of 25.4 months, the median duration of response was 22.7, and the median PFS was 18.6 months. PFS reached 30.8 and 32.9 months for patients with a CR or Cru, respectively. Interpretation: The combination of ibrutinib and bortezomib shows durable efficacy in patients with relapsed or refractory MCL, also in the presence of high-risk features. Funding: SAKK (Hubacher Fund), Swiss State Secretariat for Education, Research and Innovation, Swiss Cancer Research Foundation, and Janssen.

Perioperative Chemoimmunotherapy With Durvalumab for Muscle-Invasive Urothelial Carcinoma: Primary Analysis of the Single-Arm Phase II Trial SAKK 06/17.

PURPOSE: The integration of immunotherapy in the perioperative setting of muscle-invasive urothelial carcinoma (MIUC) appears promising. SAKK 06/17 investigated the addition of neoadjuvant durvalumab to gemcitabine/cisplatin (GC) chemotherapy followed by radical surgery and adjuvant checkpoint inhibition with durvalumab. PATIENTS AND METHODS: SAKK 06/17 was an investigator-initiated, open-label, single-arm phase II study including cisplatin-fit patients with stage cT2-T4a cN0-1 operable MIUC. Four cycles of neoadjuvant GC in combination with four cycles of durvalumab (start with GC cycle 2) were administered, followed by radical surgery. Adjuvant durvalumab was given for 10 cycles. The primary end point was event-free survival (EFS) at 2 years. RESULTS: Sixty one patients were accrued at 12 sites. The full analysis set consisted of 57 patients, 54 (95%) had bladder cancer. Median follow-up was 40 months. The primary end point was met, with EFS at 2 years of 76% (one-sided 90% CI [lower bound], 67%; two-sided 95% CI, 62 to 85). EFS at 3 years was 73% (95% CI, 59 to 83). Complete pathologic response in resected patients (N = 52) was achieved in 17 patients (33%), and 31 (60%) had pathologic response

Engineering a versatile and retrievable cell macroencapsulation device for the delivery of therapeutic proteins.

Encapsulated cell therapy holds a great potential to deliver sustained levels of highly potent therapeutic proteins to patients and improve chronic disease management. A versatile encapsulation device that is biocompatible, scalable, and easy to administer, retrieve, or replace has yet to be validated for clinical applications. Here, we report on a cargo-agnostic, macroencapsulation device with optimized features for protein delivery. It is compatible with adherent and suspension cells, and can be administered and retrieved without burdensome surgical procedures. We characterized its biocompatibility and showed that different cell lines producing different therapeutic proteins can be combined in the device. We demonstrated the ability of cytokine-secreting cells encapsulated in our device and implanted in human skin to mobilize and activate antigen-presenting cells, which could potentially serve as an effective adjuvant strategy in cancer immunization therapies. We believe that our device may contribute to cell therapies for cancer, metabolic disorders, and protein-deficient diseases.

SARS-CoV-2 m-RNA Vaccine Response in Immunocompromised Patients: A Monocentric Study Comparing Cancer, People Living with HIV, Hematopoietic Stem Cell Transplant Patients and Lung Transplant Recipients.

Immunocompromised patients (ICPs) have a higher risk of developing severe forms of COVID-19 and experience a higher burden of complications and mortality than the general population. However, recent studies have suggested that the antibody response to SARS-CoV-2 mRNA vaccines could be highly variable among different ICPs. Using a collaborative, monocentric, prospective cohort study, we assessed anti-SARS-CoV-2 spike protein antibody titers following two and three doses of mRNA vaccines in four groups of ICPs (cancer [n = 232]: hematopoietic stem cell transplant [HSCT; n = 126] patients; people living with HIV [PLWH; n = 131]; and lung transplant [LT; n = 39] recipients) treated at Geneva University Hospitals; and healthy individuals (n = 49). After primo-vaccination, the highest anti-S antibody geometric mean titer (IU/mL) was observed in healthy individuals (2417 IU/mL [95% CI: 2327-2500]), the PLWH group (2024 IU/mL [95% CI:1854-2209]) and patients with cancer (840 IU/mL [95% CI: 625-1129]), whereas patients in the HSCT and LT groups had weaker antibody responses (198 IU/mL [95% CI: 108-361] and 7.3 IU/mL [95% CI: 2.5-22]). The booster dose conferred a high antibody response after 1 month in both PLWH (2500 IU/mL) and cancer patients (2386 IU/mL [95% CI: 2182-2500]), a moderate response in HSCT patients (521 IU/mL [95% CI: 306-885]) and a poor response in LT recipients (84 IU/mL [95% CI: 18-389]). Contemporary treatment with immunosuppressive drugs used in transplantation or chemotherapy was associated with a poor response to vaccination. Our findings confirmed the heterogeneity of the humoral response after mRNA vaccines among different ICPs and the need for personalized recommendations for each of these different groups.

The Future of Cancer Immunotherapy.

This article describes three emerging, novel cancer immunotherapies: BITE, TIL and cancer vaccines are therapies that recognize specific targets on cancer cells and trigger a specific immune response. So far, not all tumor types can benefit from these approaches the best results have been observed in hematological malignancies, melanoma, and lung cancer. These novel biological products are currently being tested in several cancer centers in Switzerland, and physicians must be familiar with these procedures, as some of their patients might be treated with such therapies in the near future.

Nab-PIPAC: a phase IB study protocol of intraperitoneal cisplatin and nab-paclitaxel administered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in the treatment of advanced malignancies confined to the peritoneal cavity.

INTRODUCTION: Intraperitoneal dissemination is a major problem resulting in very poor prognosis and a rapid marked deterioration in the quality of life of patients. Pressurised intraperitoneal aerosol chemotherapy (PIPAC) is an emergent laparoscopic procedure aiming to maximise local efficacy and to reduce systemic side effects. METHODS AND ANALYSIS: Nab-PIPAC, a bicentre open-label phase IB, aims to evaluate safety of nab-paclitaxel and cisplatin association using in patients with peritoneal carcinomatosis (PC) of gastric, pancreatic or ovarian origin as ≥1 prior line of systemic therapy. Using a 3+3 design, sequential intraperitoneal laparoscopic application of nab-paclitaxel (7.5, 15, 25, 37.5, 52.5 and 70 mg/m2) and cisplatin (10.5 mg/m2) through a nebuliser to a high-pressure injector at ambient temperature with a maximal upstream pressure of 300 psi. Treatment maintained for 30 min at a pressure of 12 mm Hg and repeated4-6 weeks intervals for three courses total.A total of 6-36 patients are expected, accrual is ongoing. Results are expected in 2024.The primary objective of Nab-PIPAC trial is to assess tolerability and safety of nab-paclitaxel and cisplatin combination administered intraperitoneally by PIPAC in patients with PC of gastric, pancreatic or ovarian origin. This study will determine maximum tolerated dose and provide pharmacokinetic data. ETHIC AND DISSEMINATION: Ethical approval was obtained from the ethical committees of Geneva and Vaud (CCER-2018-01327). The study findings will be published in an open-access, peer-reviewed journal and presented at relevant conferences and research meetings. TRIAL REGISTRATION NUMBER: NCT04000906.

Immortalized human myoblast cell lines for the delivery of therapeutic proteins using encapsulated cell technology.

Despite many promising results obtained in previous preclinical studies, the clinical development of encapsulated cell technology (ECT) for the delivery of therapeutic proteins from macrocapsules is still limited, mainly due to the lack of an allogeneic cell line compatible with therapeutic application in humans. In our work, we generated an immortalized human myoblast cell line specifically tailored for macroencapsulation. In the present report, we characterized the immortalized myoblasts and described the engineering process required for the delivery of functional therapeutic proteins including a cytokine, monoclonal antibodies and a viral antigen. We observed that, when encapsulated, the novel myoblast cell line can be efficiently frozen, stored, and thawed, which limits the challenge imposed by the manufacture and supply of encapsulated cell-based therapeutic products. Our results suggest that this versatile allogeneic cell line represents the next step toward a broader development and therapeutic use of ECT.

Fibroblast growth factor receptor (FGFR) inhibitor rogaratinib in patients with advanced pretreated squamous-cell non-small cell lung cancer over-expressing FGFR mRNA: The SAKK 19/18 phase II study.

BACKGROUND: Patients with advanced squamous-cell lung cancer (SQCLC) frequently (46%) exhibit tumor overexpression of fibroblast growth factor receptor (FGFR) messenger ribonucleic acid (mRNA). Rogaratinib is a novel oral pan-FGFR inhibitor with a good safety profile and anti-tumor activity in early clinical trials as a single agent in FGFR pathway-addicted tumors. SAKK 19/18 determined clinical activity of rogaratinib in patients with advanced SQCLC overexpressing FGFR1-3 mRNA. METHODS: Patients with advanced SQCLC failing standard systemic treatment and with FGFR1-3 mRNA tumor overexpression as defined in the protocol received rogaratinib 600 mg BID until disease progression or intolerable toxicity. A 6-months progression-free survival rate (6mPFS) ≤15 % was considered uninteresting (H0), whereas a 6mPFS ≥38 % was considered promising (H1). According to a Simon 2-stage design, 2 out of 10 patients of the first stage were required to be progression-free at 6 months. Comprehensive Genomic Profiling was performedusing the Oncomine Comprehensive Assay Plus (Thermo Fisher Scientific). RESULTS: Between July 2019 and November 2020, 49 patients were screened and 20 were classified FGFR-positive. Among a total of 15 patients, 6mPFS was reached in 1 patient (6.7 %), resulting in trial closure for futility after the first stage. There were 7 (46.7 %) patients with stable disease and 5 (33.3 %) patients with progressive disease. Median PFS was 1.6 (95 % CI 0.9-3.5) months and median overall survival (OS) 3.5 (95 % CI 1.0-5.9) months. Most frequent treatment-related adverse events (TRAEs) included hyperphosphatemia in 8 (53 %), diarrhea in 5 (33 %), stomatitis in 3 (20 %) and nail changes in 3 (20 %) patients. Grade ≥3 TRAEs occurred in 6 (40 %) patients. No associations between mutational profile and treatment outcome were observed. CONCLUSION: Despite preliminary signals of activity, rogaratinib failed to improve PFS in patients with advanced SQCLC overexpressing FGFR mRNA. FGFR inhibitors in SQCLC remain a challenging field, and more in-depth understanding of pathway crosstalks may lead to the development of drug combinations with FGFR inhibitors resulting in improved outcomes.

Outcome and Prognostic Factors of COVID-19 Infection in Swiss Cancer Patients: Final Results of SAKK 80/20 (CaSA).

Purpose: These are the final results of a national registry on cancer patients with COVID-19 in Switzerland. Methods: We collected data on symptomatic COVID-19-infected cancer patients from 23 Swiss sites over a one-year period starting on 1 March 2020. The main objective was to assess the outcome (i.e., mortality, rate of hospitalization, ICU admission) of COVID-19 infection in cancer patients; the main secondary objective was to define prognostic factors. Results: From 455 patients included, 205 patients (45%) had non-curative disease, 241 patients (53%) were hospitalized for COVID-19, 213 (47%) required oxygen, 43 (9%) invasive ventilation and 62 (14%) were admitted to the ICU. Death from COVID-19 infection occurred in 98 patients, resulting in a mortality rate of 21.5%. Age ≥65 years versus <65 years (OR 3.14, p = 0.003), non-curative versus curative disease (OR 2.42, p = 0.012), ICU admission (OR 4.45, p < 0.001) and oxygen requirement (OR 20.28, p < 0.001) were independently associated with increased mortality. Conclusions: We confirmed high COVID-19 severity and mortality in real-world cancer patients during the first and second wave of the pandemic in a country with a decentralized, high-quality, universal-access health care system. COVID-19-associated mortality was particularly high for those of older age in a non-curative disease setting, requiring oxygen or ICU care.

SAKK 35/15: a phase 1 trial of obinutuzumab in combination with venetoclax in patients with previously untreated follicular lymphoma.

This phase 1 study evaluated safety, tolerability, and preliminary efficacy of obinutuzumab in combination with venetoclax in patients with previously untreated grade 1-3a follicular lymphoma in need of systemic therapy. Two DLs of venetoclax were evaluated with an expansion cohort at the recommended phase 2 dose. Twenty-five patients were enrolled. The recommended phase 2 dose was venetoclax 800 mg OD continuously for 6 cycles starting on day 2 of cycle 1, with obinutuzumab 1000 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2 to 6, followed by obinutuzumab maintenance every 2 months for 2 years. Only 1 patient had a DLT consisting of grade 4 thrombocytopenia after the first obinutuzumab infusion. Neutropenia was the most common adverse event of grade ≥3 at least possibly attributed to study treatment. Twenty-four patients were evaluable for response after cycle 6 by computed tomography (CT) and 19 by positron emission tomography/CT (PET/CT): overall and complete response rates were 87.5% (95% CI, 67.6% to 97.3%) and 25% (95% CI, 9.8% to 46.7%) in the CT-evaluated patients and 84.2% (95% CI, 60.4% to 96.6%) and 68.4% (95% CI, 43.4% to 87.4%), respectively, in the PET/CT-evaluated patients. One-year progression-free survival was 77.8% (95% CI, 54.6% to 90.1%) and 79% (95% CI, 47.9% to 92.7%) for CT and PET/CT-evaluable patients, respectively, whereas progression-free survival at 30 months was 73.2% (95% CI, 49.8%, 87.0%) as assessed by CT and 79.0% (95% CI, 47.9%, 92.7%) by PET/CT. Despite the activity observed, our results do not support further development of the combination in this patient population. This trial was registered at www.clinicaltrials.gov as #NCT02877550.

Complementary and Integrative Medicine in Pediatric Oncology - Development and Evaluation of a Blended Learning Program.

BACKGROUND: A blended learning program to promote the consultation expertise of pediatric oncologists (POs) on complementary and integrative medicine (CIM) was developed and completed by POs as part of a training program. A previous study indicated that POs in Germany were in need of information and training on CIM, and that there were no medical training offers on the subject in Germany. METHODS: Evaluation of e-learning (questionnaires) and practically oriented one-day, face-to-face workshops (questionnaires, simulation patients), the workshops were evaluated with regard to changes in quality of physician-patient interaction and with regard of the participants' feedback. RESULTS: 32 POs signed up for the program and completed the e-learning. 22 POs participated in one of the workshops. POs agreed that they had received professionally relevant content during the e-learning. The questionnaires on physician-patient interaction showed neither clear positive nor negative changes concerning the quality of interaction. The feedback from the participants on the workshop was very positive. CONCLUSION: Following the end of the blended learning program the e-learning was made available again for interested POs. 34 further applications were received for participation in this part of the training program. With around 300 POs in Germany, this shows a high demand for further training offers of this kind as well as a need for further development.

Humoral and cellular immunogenicity two months after SARS-CoV-2 messenger RNA vaccines in patients with cancer.

Little is known on the long-lasting humoral response and the T cell activation induced by SARS-CoV-2 mRNA vaccines in patients with cancer. The study assessed the efficacy of the SARS-CoV-2 mRNA vaccines through measuring the seroconversion rate at pre-specified time points and the effect on the T cell immunity in patients with cancers. The study included 131 adult patients with solid or hematological cancer, who received SARS-CoV-2 mRNA vaccines. 96.2% of them exhibited adequate antibody response to the SARS-CoV-2 mRNA vaccines 2 months after the booster dose. SARS-CoV-2 mRNA vaccines could induce T cell activation; however, this is more likely in patients who have a positive seroconversion (94%) compared with the patients who did not (50%). Further research into the clinical relevance of low antibodies titers and lack of T cell activity is required to set up an effective vaccination strategy within this group of patients.