Evaluation of the frailty characteristics and clinical outcomes according to the new frailty-based outcome prediction model (Myeloma Risk Profile-MRP) in a UK real-world cohort of elderly newly diagnosed Myeloma patients

The management of myeloma in the elderly is shifting its focus towards reducing the risk of under-treating fit patients and the risk of over-treating frail patients. Frailty assessment is required in this patient group in order to individualise treatment decisions. In addition to the proven prognostic values of the International Myeloma Working Group (IMWG) frailty score and the revised Myeloma Co-morbidity Index (R-MCI), a new easy-to-use frailty-based risk profile score (high-risk (i.e. frail), medium risk (i.e. intermediate-fitness) and low-risk (i.e. fit)) named Myeloma Risk Profile (MRP) was shown to be predictive of survival in the clinical trial setting. In this retrospective real-world study, we set out to evaluate the frailty characteristics and clinical outcomes according to the different MRP scoring algorithm categories (frail vs. intermediate vs fit), in a high risk cohort of elderly newly diagnosed myeloma patients treated with the fixed-duration triplet therapy VCD (bortezomib with cyclophosphamide and dexamethasone). Clinical outcomes included: reason for treatment discontinuation, overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse events (AEs). Out of 100 patients, 62 were frail, 27 were intermediate and 11 were fit, according to MRP scores. To enable meaningful comparisons between comparable numbers, subgroups analyses for ORR, OS, PFS, and AEs focused on frail (n = 62) versus intermediate or fit (n = 38) patients. The proportion of patients in each subgroup who were able to complete the planned course of treatment was (frail: 43.5% vs. intermediate or fit: 55.3%). A higher proportion in the frail subgroup discontinued therapy due to progressive disease (19.4% vs. 2.6%). Discontinuation due to toxicity was comparable across subgroups (14.5% vs. 15.8%), ORR in the total cohort was 75%, and this was comparable between subgroups (frail: 74.2% vs. intermediate or fit: 76.3%). There was a trend for a shorter median OS in the frail subgroup but without a statistical significance: (frail vs. intermediate or fit): (46 months vs. not reached, HR: 1.94, 95% CI 0.89–4.2, p = 0.094). There was no difference in median PFS between subgroups: (frail vs. intermediate or fit): (11.8 vs. 9.9 months, HR: 0.99, 95% CI: 0.61–1.61, P = 0.982). This cohort demonstrated a higher incidence rate of AEs in frail patients compared to those in the intermediate or fit group: patients with at least one any grade toxicity (85.5% vs. 71.1%), patients with at least one ≥G3 AE (37.1% vs. 21.1%). In conclusion, our study is to the first to evaluate clinical outcomes according to MRP in a high risk real-world cohort of patients treated exclusively with the proteasome inhibitor-based VCD therapy. Our study demonstrated a trend for worse OS in addition to worse AE outcomes in the frail group, but no difference in PFS with this fixed-duration therapy. MRP is an easy-to-use tool in clinical practice; its prognostic value was validated in the real-world in a large cohort of patients from the Danish Registry. Further evaluation of MRP in the real-world when continuous therapies are used, can further support the generalisability of its prognostic value in elderly myeloma patients.

Test to release from isolation after testing positive for SARS-CoV-2

The rapid spread and high transmissibility of the Omicron variant of SARS-CoV-2 is likely to lead to a significant number of key workers testing positive simultaneously. Under a policy of self-isolation after testing positive, this may lead to extreme staffing shortfalls at the same time as e.g. hospital admissions are peaking. Using a model of individual infectiousness and testing with lateral flow tests (LFT), we evaluate test-to-release policies against conventional fixed-duration isolation policies in terms of excess days of infectiousness, days saved, and tests used. We find that the number of infectious days in the community can be reduced to almost zero by requiring at least 2 consecutive days of negative tests, regardless of the number of days' wait until testing again after initially testing positive. On average, a policy of fewer days' wait until initiating testing (e.g 3 or 5 days) results in more days saved vs. a 10-day isolation period, but also requires a greater number of tests. Due to a lack of specific data on viral load progression, infectivity, and likelihood of testing positive by LFT over the course of an Omicron infection, we assume the same parameters as for pre-Omicron variants and explore the impact of a possible shorter proliferation phase.

Mental Health Assist and Diagnosis Conversational Interface using Logistic Regression Model for Emotion and Sentiment Analysis

The aim of this work was to create a fully functional AI-ML based conversational agent that behaves like a real time therapist which analyses the user’s emotion at every step and provides appropriate responses and feedback. AI chatbots, although fairly new to the domain of mental health, can help in destigmatizing seeking help, and are more easily accessible to everyone, at any time. Chatbots provide an effective way to communicate with a user and offer helpful emotional support in a more economical way. While making regular psychiatric visits often require a fixed duration/appointment which can be time consuming and is restricted to a fraction of the day, the proposed chatbot can keep track of your health on the go at any time. The application will have a self-healing kit suggesting various exercises, both mental and physical that the user may implement in his day-to-day life. The study below goes into further detail on the major insinuations for future chatbot agent design and assessment

Frontline treatment in CLL: the case for time-limited treatment

Over the last decade, the advent of Bruton tyrosine kinase inhibitors (BTKi) has profoundly modified the therapeutic strategy in chronic lymphocytic leukemia (CLL), introducing the concept of treatment until progression. Initially, the bcl-2 inhibitor venetoclax (VEN) was used as a single agent and then was rapidly combined in VEN-based regimens associated with either anti-CD20 or with BTKi. These regimens yielded a high rate of complete remission, leading to their use as a fixed duration treatment. The decision between continuous treatment with BTKi and VEN-based combinations relies mostly on comorbidities, comedications, and patient/physician preferences. Notably, with BTKi, cardiovascular comorbidities, hypertension, and potential pharmacological interactions should be carefully evaluated. On the other hand, the risk of tumor lysis syndrome with VEN should be monitored at treatment initiation. TP53 alteration and IGHV mutational status should also be assessed, as they remain important for therapeutic decisions. Fit patients with a TP53 wild type and IGHV-mutated CLL may still benefit from fludarabine-cyclophosphamide-rituximab chemoimmunotherapy (CIT), as it may result in a very long remission duration. VEN-based treatments are well tolerated, and no additional toxicity has been observed when combined with anti-CD20 or BTKi. The 1-year fixed-duration association of VEN plus obinutuzumab was evaluated in frontline for older adult patients. Nonetheless, considering the favorable outcome, an extension of indication for fit younger patients is expected. The association of VEN and BTKi is promising, even if the follow-up is still short. It is currently being tested against CIT, BTKi continuous treatment, and VEN plus anti-CD20.

BRUIN CLL-322: A Phase 3 Open-Label, Randomized Study of Fixed Duration Pirtobrutinib Plus Venetoclax and Rituximab Versus Venetoclax and Rituximab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (Trial in Progress)

Background: Covalent Bruton's Tyrosine Kinase (BTK) inhibitors (BTKi) have transformed the management of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but these treatments are not curative and the majority of patients will require additional treatment. The MURANO study established the time-limited combination of 2 years venetoclax plus rituximab as a clinically important regimen for patients with R/R CLL/SLL. However, that trial almost exclusively enrolled patients who were never treated with a covalent BTKi, a population less relevant in the context of today's standard of care. Pirtobrutinib is a highly selective, non-covalent BTKi that inhibits both wild type (WT) and C481-mutated BTK with equal low nM potency. In a phase 1/2 BRUIN trial, pirtobrutinib achieved pharmacokinetic exposures that exceeded its BTK IC96 at trough, was well tolerated, and demonstrated promising efficacy in CLL/SLL patients regardless of prior therapy, number of prior lines of therapy, or BTK C481 mutation status (Mato et al. Lancet 2021;397,10277:892-901). Therefore, adding fixed duration pirtobrutinib to the time-limited MURANO regimen may allow for even deeper and more prolonged disease control, and generate a clinically relevant dataset in a BTK-pretreated CLL/SLL population. Study Design and Methods: BRUIN CLL-322 is a randomized, open-label, global phase 3 study comparing fixed duration pirtobrutinib plus venetoclax and rituximab (PVR) versus venetoclax and rituximab (VR) in patients with CLL/SLL who have received prior therapy. To ensure relevance in the modern therapy context, a minimum of 80% of patients must have had a prior covalent BTKi. Approximately 600 patients will be randomized 1:1. Randomization will be stratified by 17p deletion (yes/no) and prior BTKi experience (discontinuation due to progressive disease vs due to other reasons vs no prior BTKi exposure). Eligible patients are adults with a diagnosis of CLL/SLL and requirement for therapy per iwCLL 2018 criteria who have received prior therapy that may or may not include a covalent BTKi. Unlimited number of lines of prior therapy are allowed. Key exclusion criteria include CNS involvement by CLL/SLL, Richter transformation at any time pre-enrollment, history of allogeneic stem cell transplant (SCT) or autologous SCT or chimeric antigen receptor (CAR) T-cell therapy within 60 days and prior therapy with a BCL2 inhibitor or non-covalent BTKi. The primary endpoint is progression-free survival (PFS) per iwCLL assessed by an independent review committee (IRC). Secondary endpoints include overall response rate (ORR), overall survival (OS), time to next treatment (TTNT), event-free survival (EFS), safety and tolerability, and patient-reported outcomes. This global study is currently enrolling patients (NCT04965493). Disclosures Mato: MSKCC: Current Employment; AstraZeneca: Consultancy; Nurix: Research Funding; AbbVie: Consultancy, Research Funding; Sunesis: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; LOXO: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; Genmab: Research Funding; DTRM BioPharma: Consultancy, Research Funding; Johnson and Johnson: Consultancy, Research Funding; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Genentech: Consultancy, Research Funding. Wierda: GSK/Novartis: Research Funding; Xencor: Research Funding; Genentech: Research Funding; Janssen: Research Funding; Cyclacel: Research Funding; Loxo Oncology, Inc.: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Karyopharm: Research Funding; Oncternal Therapeutics, Inc.: Research Funding; Miragen: Research Funding; Sunesis: Research Funding; KITE Pharma: Research Funding; Juno Therapeutics: Research Funding; Acerta Pharma Inc.: Research Funding; Gilead Sciences: Research Funding; Genzyme Corporation: Consultancy; AbbVie: Research Funding; AstraZeneca: Research Funding. Pagel: Pharmacyclics/AbbVie: Consultancy; Gilead: Consultancy; Epizyme: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; MEI Pharma: Consultancy; Kite, a Gilead Company: Consultancy; Incyte/MorphoSys: Consultancy; Actinium Pharmaceuticals: Consultancy. Davids: Astra-Zeneca: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; AbbVie: Consultancy; Adaptive Biotechnologies: Consultancy; BeiGene: Consultancy; Celgene: Consultancy; Eli Lilly and Company: Consultancy; MEI Pharma: Consultancy; Merck: Consultancy; Research to Practice: Consultancy; Takeda: Consultancy; MEI Pharma: Consultancy, Research Funding; Janssen: Consultancy; Genentech: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; Ascentage Pharma: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Surface Oncology: Research Funding. Zinzani: ROCHE: Other, Speakers Bureau; KYOWA KIRIN: Other, Speakers Bureau; BMS: Other: Advisory board, Speakers Bureau; SERVIER: Other: Advisory board, Speakers Bureau; VERASTEM: Consultancy, Other: Advisory board, Speakers Bureau; SANDOZ: Other: Advisory board; NOVARTIS: Consultancy, Other, Speakers Bureau; Incyte: Other, Speakers Bureau; ADC Therap.: Other; MSD: Consultancy, Other: Advisory board, Speakers Bureau; JANSSEN-CILAG: Other: Advisory board, Speakers Bureau; TAKEDA: Other: Advisory board, Speakers Bureau; EUSAPHARMA: Consultancy, Other, Speakers Bureau; GILEAD: Other: Advisory board, Speakers Bureau; Beigene: Other, Speakers Bureau; TG Therapeutics: Other: Advisory board, Speakers Bureau; CELLTRION: Other: Advisory board, Speakers Bureau. Lu: Eli Lilly and Company: Current Employment, Current equity holder in publicly-traded company. Liu: Loxo Oncology at Lilly: Current Employment; AstraZeneca: Ended employment in the past 24 months. Shahda: Loxo Oncology at Lilly: Current Employment, Current equity holder in publicly-traded company. Leow: Loxo Oncology at Lilly: Current Employment, Current equity holder in publicly-traded company. Tam: Beigene: Honoraria; Loxo: Honoraria; Abbvie: Research Funding; Janssen: Research Funding; Beigene: Research Funding; Janssen: Honoraria; Abbvie: Honoraria. Woyach: AbbVie Inc, ArQule Inc, Janssen Biotech Inc, AstraZeneca, Beigene: Other: Advisory Committee; AbbVie Inc, ArQule Inc, AstraZeneca Pharmaceuticals LP, Janssen Biotech Inc, Pharmacyclics LLC, an AbbVie Company,: Consultancy; AbbVie Inc, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company: Research Funding; Gilead Sciences Inc: Other: Data & Safety. Eyre: Secura Bio: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria, Other: Travel to conferences; AstraZeneca: Honoraria, Research Funding; Janssen: Honoraria; Gilead/KITE: Honoraria, Other: Travel support for conferences, Research Funding, Speakers Bureau; Incyte: Consultancy; Loxo Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria; Beigene: Honoraria, Research Funding.

Fixed Duration Combination Therapy with Ibrutinib (ibr) and Venetoclax (ven) Leads to Deep Responses in Relapsed/Refractory (rel/ref) Chronic Lymphocytic Leukemia (CLL): Results of a Phase 2 Study

Introduction: Ibr and ven are 1 st generation BTK and BCL2 inhibitors respectively that are approved for use in patients with CLL. They are both oral agents that have been shown to work synergistically together with no unexpected toxicities beyond what is already known about each of them. Their combination is very effective in the frontline treatment of CLL including fixed duration therapy for 15 cycles which produces high complete remissions (CR) and undetectable minimal residual disease (uMRD) rates as well as high progression free survival (PFS) and overall survival (OS) independent of high-risk features [Allen JH, et al. EHA virtual annual meeting 2021; Jain N, et al N Engl J Med 2019]. There is also data to support the use of this combination in the rel/ref setting [Hillmen P, et al. J Clin Oncol 2019] and here we present results of a phase 2 trial of fixed duration therapy with ibr+ven in rel/ref CLL (NCT03045328). Methods: Patients with rel/ref CLL with indications for treatment were enrolled at Stanford Cancer Institute and City of Hope National Medical Center. Treatment was initiated with ibr monotherapy (420mg daily) for 8 weeks after which ven ramp up was introduced. Ven was escalated to full dose (400mg daily) over 5 weeks and the combination of ibr+ven was then continued for a total of 2 years. Treatment was stopped in all patients at week 118 and all patients were evaluated 30 days later to complete study follow up. The primary endpoint was the assessment of CR rate at week 62. Secondary endpoints included overall response rate (ORR), duration of response (DOR), PFS, OS, evaluation of adverse events (AEs), as well as rate of uMRD in the bone marrow at week 62 and week 117 of treatment by flow cytometry (10 -4 sensitivity [uMRD4]) and Clonoseq sequencing (10 -6 sensitivity [uMRD6]). Results: A total of 22 patients were enrolled. Median age of the patients was 68 (range 39-82 years). Median prior treatment regimens were 1 (range 1-3). Eleven patients received prior FCR as 1 st line therapy, 9 received BR, 1 received FR, and 1 had received rituximab alone. None had prior BTK inhibitor or ven. Baseline characteristics are shown in Table 1. Twenty-one patients initiated ven. One patient withdrew consent prior to the start of ven. Eighteen patients completed full trial treatment. Three patients discontinued treatment for these reasons: Hodgkin's transformation, kidney failure, need for a coronary stent. Five patients interrupted dosing due to toxicity and five patients had dose reductions. Three patients reduced ibrutinib, 2 due to rash and 1 due to recurrent atrial fibrillation, and 5 patients reduced ven due to fatigue, neutropenia (2), or diarrhea (2). CR rate (intention to treat [n=22]) at week 62 was 55% while the ORR was 91%. PFS and OS were 95% and 100% at 2 years. After 1 year of combination therapy, 13 of 20 (65%) evaluable patients had achieved bone marrow uMRD4 (5 positive and 2 not done) and 4 of 20 (20%) achieved bone marrow uMRD6. After 2 years, 2 additional patients achieved bone marrow uMRD4 (15 of 20 [75%]). Bone marrow flow and Clonoseq MRD data were available in 13 patients at the end of study. Eight were undetectable by flow and Clonoseq (uMRD6), 3 by flow only (uMRD4), and 2 were positive with both (MRD+). Seven patients experienced 11 serious AEs attributed to treatment: 3 with sepsis, 3 pneumonia, 2 atrial fibrillation, and 1 each diarrhea, dehydration, and pulmonary embolism. AEs ≥ Grade 3 are shown in Table 2. There were no TLS events. Conclusions: Ibr+ven combination for a fixed duration of 2 years after initial ibrutinib lead in is a well-tolerated, effective, oral, targeted therapy regimen for patients with rel/ref CLL. Most patients achieve an uMRD4 response in the bone marrow. The effect of poor risk features of disease and dose interruptions on depth of response will be reported. Figure 1 Figure 1. Disclosures Siddiqi: Janssen: Speakers Bureau; Oncternal: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pharmacyclics LLC, an AbbVie Company: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Kite Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Juno Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Research Funding. Coutre: Acerta: Other: Data Safety Monitoring Committee, Research Funding; Genentech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Beigene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Data Safety Monitoring Committee, Research Funding; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Evaluating Patients' Preferences Regarding Treatment Options for Waldenström's Macroglobulinemia, a Discrete-Choice-Experiment

Introduction The management of Waldenström's Macroglobulinemia (WM), a rare and incurable B-cell non-Hodgkin lymphoma, has evolved in recent years. Treatment options are increasing including more modern targeted therapies. Therefore there are currently several effective treatment options available for WM. There is no consensus on a preferred treatment. Widely used treatment options include rituximab combined with chemotherapy, proteasome inhibitors, and the oral BTK inhibitor ibrutinib. These treatments have varying properties in terms of efficacy, toxicity profile, duration (fixed-duration vs long-term maintenance), administration (oral vs intravenous/subcutaneous (IV/SC)), and type of agent (chemotherapy vs targeted therapy). A better understanding of patients' treatment preferences could aid physicians in developing an individualized treatment plan. Also, a better insight in patients' treatment views could help direct future clinical studies in WM. However, treatment preferences of WM patients have not been investigated. We aimed to evaluate treatment preferences of WM patients by means of a discrete choice experiment (DCE) and to assess the importance of different attributes describing the currently available treatment regimens. Methods A mixed-method approach, consisting of a literature review, qualitative interviews and expert discussions was utilized for identification and selection of attributes/levels. A DCE questionnaire was developed in Dutch and included 5 treatment-related attributes: 5-year progression-free survival (PFS), frequency/route of administration(IV/SC or oral)/setting (clinic or home) of treatment, adverse events (nausea & vomiting and fatigue, neuropathy and atrial fibrillation), risk of future secondary malignancies (low vs high), and type of treatment agent (chemotherapy or targeted therapy). Each respondent was presented with 16 choice cards and was asked to choose between two hypothetical but realistic treatment options (see Figure 1 for an example). A pilot DCE study was carried out in 5 patients to evaluate feasibility. Data were collected via a nationwide online questionnaire via the patient organizations' website and via paper-based questionnaires sent to the participants known at the outpatient clinic. An orthogonal design was used to construct the choice tasks and a mixed logit panel data model was used to assess patients' preferences and trade-offs between attributes/levels. Results A total of 330 online questionnaires and 17 paper-based questionnaires were returned. After excluding incomplete survey data, 214 (65%) questionnaires were included for data analysis, respondents characteristics are presented in Table 1. The 5-year PFS followed by the risk of secondary malignancies were the most important attributes for making treatment decisions. The probability of choosing a treatment option increased with 26% and 22% if the 5-year PFS increased from 50% to 70% and if the chance of future secondary malignancies was decreased from "high risk" to "low risk", respectively. Of the adverse events, patients disliked being at risk for neuropathy the most more than nausea, vomiting and extreme fatigue. Patients were willing to give up 7,2% treatment efficacy to avoid risk of neuropathy. The probability of choosing a treatment option increased with 8% for a fixed-duration treatment with IV/SC administration at the hospital compared to an ongoing daily oral regimen at home (Table 2). Socio-demographic characteristics such as age, gender and treatment status did not significantly influence patients' preferences with the exception of educational status. Lower 5-year PFS was more acceptable for patients with higher education (P<0.0001 ) and this subgroup of patients preferred a treatment with targeted therapy and low risk of secondary malignancy (P<0.0001). Conclusion These are the first data on WM patients' preferences on treatment characteristics. We found that Dutch WM patients find efficacy (high 5-year PFS rate) the most important attribute, followed by a low risk of future secondary malignancies. Neuropathy was the adverse event they most wanted to avoid. They preferred a fixed-duration IV/SC treatment over an ongoing oral regimen. These data can be used in discussions with individual patients about their treatment preference, and help direct future clinical trials that optimally connect to WM patients' preferences. Figure 1 Figure 1. Disclosures Minnema: Cilag: Consultancy; Janssen: Consultancy; Celgene: Other: Travel expenses; Alnylam: Consultancy; BMS: Consultancy; Kite/Gilead: Consultancy. Kersten: Miltenyi Biotec: Consultancy, Honoraria, Other: Travel support; Roche: Consultancy, Honoraria, Other: Travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: Travel support; BMS/Celgene: Consultancy, Honoraria; Takeda: Research Funding; Celgene: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding. Vos: Celgene: Other: Travel reimbursement; Sanofi: Membership on an entity's Board of Directors or advisory committees.

Minimal Residual Disease Assessment in CLL/SLL: Is It Ready for Routine Clinical Practice?

Minimal residual disease (MRD) in chronic lymphocytic leukemia (CLL) is defined as <1 CLL cell per 10,000 leukocytes (0.01%; <10−4). Flow cytometry and next-generation sequencing have demonstrated high sensitivity in MRD detection. MRD assessment may help to determine prognosis after fixed-duration regimens; this has been established in the contexts of chemoimmunotherapy and venetoclax/antibody combinations. In the short term, MRD status does not seem to inform prognosis in patients treated with a BTK inhibitor plus venetoclax-based regimens; however, long-term data will be needed to determine whether it is beneficial in this population. Numerous trials have demonstrated that MRD may be used to guide therapy. It is unclear whether using an MRD-guided treatment strategy is better than using fixed-duration therapy; ongoing and future studies are warranted.

On a discrete game problem with non-convex control vectograms

In a normed space of finite dimension, a discrete game problem with fixed duration is considered. The terminal set is determined by the condition that the norm of the phase vector belongs to a segment with positive ends. In this paper, a set defined by this condition is called a ring. At each moment, the vectogram of the first player's controls is a certain ring. The controls of the second player at each moment are taken from balls with given radii. The goal of the first player is to lead a phase vector to the terminal set at a fixed time. The goal of the second player is the opposite. In this paper, necessary and sufficient termination conditions are found, and optimal controls of the players are constructed.