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We present a case of a rare lymphoproliferative disease diagnosed while differentiating between the causes of exudative-constrictive pericarditis. An 83-year old man was hospitalized with shortness of breath, edema and newly diagnosed atrial fibrillation (AF). Initially, the signs and symptoms were interpreted as manifestations of heart failure due to old myocardial infarction, arterial hypertension and AF. However, no significant systolic or diastolic dysfunction of the left ventricle and valve disease were identified and natriuretic peptide level was normal. Despite treatment, dyspnea and edema persisted, and pleural effusion (requiring drainage) and pericardial effusion increased. Repeated echocardiography showed signs of exudative-constrictive pericarditis. We consequently excluded the infectious (tuberculosis) and non-infectious (electrolyte disorders, hypothyroidism, solid tumors) etiologies of effusion. Taking into account the long-standing mediastinal lymphadenopathy (the patient had been previously examined, but the cause not identified), anemia, episodes of low-grade fever, weight loss, and polyneuropathy, a lymphoproliferative disease was suspected. Serum protein electrophoresis identified an M spike in the gamma globulin region. Immunophenotyping of peripheral blood lymphocytes and immunohistochemical examination of bone marrow confirmed the diagnosis of mantle cell lymphoma. The patient was referred for specialized treatment. At 5 months of the follow-up, the therapy was successful, the patient was stable with no cardiac complaints, no edema, and no new AF episodes. The case demonstrates the need to strictly follow differential diagnostic algorithms to identify the causes of nonspecific symptoms beyond one medical specialty.

Objective: to conduct a clinical and economic study of acalabrutinib for the treatment of adult patients with relapsed/refractory form of mantle cell lymphoma who previously received at least one line of therapy in the Russian Federation.Material and methods. Acalabrutinib and ibrutinib were considered as compared treatment options. Based on the adjusted indirect comparison, they were found to be comparable in terms of overall survival and progression-free survival. Therefore, a cost minimization analysis method was selected for the study. Based on results of ACE-LY-004 clinical trial a distributed survival model was developed. The model was used to calculate drug costs over a 3-year horizon. To explore uncertainty in the results of economic evaluations we conducted a sensitivity analysis. A number of patients in the hypothetical cohort who could be further treated with a less expensive drug was determined during a missed opportunity analysis. Both mean life years gained and mean progression-free life years were calculated too.Results. Based on simulations over a 3-year horizon, the mean life years gained were 2.45, and the mean progression-free life years were 1.75. The average costs of acalabrutinib therapy both over 1 year and in total over 3 years were 36.6% lower compared to ibrutinib. So, in the 1st year, the costs for acalabrutinib were 3,546,237,60 rubles, for ibrutinib – 5,591,391,00 rubles (a difference of 2,045,153,40 rubles). Using acalabrutinib for 3 years was associated with costs of 7,252,980,60 rubles compared to 11,435,852,60 rubles for ibrutinib (a decrease of 4,182,872,00 rubles). Univariate multi-way sensitivity analysis showed the robustness of modeling results to price fluctuations in the range ±10%. For a hypothetical cohort of 100 patients, using acalabrutinib instead of the more expensive ibrutinib within the same budget will provide therapy to additional 57 patients per year.Conclusion. The results of the study demonstrated that acalabrutinib compared to ibrutinib for the treatment of adult patients with relapsed/ refractory form of mantle cell lymphoma can reduce costs for the 1st year of therapy by 2,045,153,40 rubles (36.6%), and by 4,182,872,00 rubles (36.6%) for 3 years. Thus, acalabrutinib is the cost-saving option for previously treated adult patients with relapsed/refractory mantle cell lymphoma in the Russian Federation.

On September 30, 2023, a discussion of the results of the European Community study on mantle cell lymphoma – TRIANGLE study was held in Moscow. The TRIANGLE phase III international randomized trial enrolled nearly 900 young subjects (up to 65 years of age) with histologically confirmed untreated mantle cell lymphoma in advanced stages II–IV. Study centers from 14 European countries participated in the study. According to the TRIANGLE study results, adding ibrutinib to autologous hematopoietic stem cell transplantation allows achieving a 3-year disease-free survival rate of 88%, which is significantly better than in the standard chemotherapy group.

Background. Mantle cell lymphoma (MCL) is a rare and clinically aggressive lymphoma subtype. Current approaches have greatly improved patients outcomes, but relapse is inevitable. In phase IIIII clinical trials, ibrutinib has shown significant activity in patients with relapsed or refractory (R/R) MCL. Aim. To assess efficacy and toxicity of ibrutinib monotherapy in patients with R/R MCL in routine practice outside of clinical trials. Materials and methods. The study enrolled patients with confirmed R/R MCL who had received at least one line of previous chemotherapy. ECOG 24, cytopenia, infectious complications, hemorrhagic syndrome were not exclusion criteria. Patients received daily oral ibrutinib 560 mg until progression or unacceptable toxicity. Results. From May 2015 to September 2020 ibrutinib therapy was started in 106 patients with R/R MCL in 16 regions of Russia. The median age was 66 years; ECOG2 18%, blastoid variant (or Ki6740% or WBC50109/l) 43%. The median number of previous treatment lines was 2 (111). The ORR was 78.4% (CRR 27.4%). The median PFS was 13.6 months and OS 23.2 months. In the blastoid group the median PFS was 4.4 months vs 36.5 months in the alternative group (p0.001), the median OS 9.0 vs 41.0 (p=0.001). The median OS of patients after progression on ibrutinib was 3.2 months. The common complications are hemorrhages (63%), diarrhea (62%), myalgia and muscle cramps (60%), infections (31%), skin and nail toxicity 15%, arrhythmia 8%. None of recipients had to completely discontinue ibrutinib therapy due to complications. Conclusion. Ibrutinib is effective and well tolerated in routine practice of R/R MCL treatment and our results are consistent with international clinical trials. The favorable toxicity profile and the high response rate made it possible to prescribe ibrutinib in severe somatic status, cytopenia, and even in the presence of infectious complications.

The prevalence of multiple primary tumors has significantly increased last time. The question of choosing the optimal tactics of therapy today not fully resolved. Particular interest is the simultaneous detection of two neoplasms of similar origin in one study biopsy material. This publication presents a case of simultaneous diagnosis of myeloid sarcoma and mantle cell lymphoma in a 65-year-old patient, which required use of two different chemotherapy protocols. This example shows the need to use an extended diagnostic approach at all stages of the therapy, which allows choosing right tactics of therapy and achieving complete remission of two neoplasms.

The meeting of the expert council concerning the application of new highly selective inhibitor of Brutons tyrosine kinase zanubrutinib in the treatment of patients with relapsed/refractory mantle cell lymphoma was held in Moscow on April 21, 2021. The leading Russian experts in the field of oncohematology took part in the meeting.

Mantle cell lymphoma. Clinical recommendations

Mantle cell lymphoma is a rare subtype of non- Hodgkin lymphoma with life-threatening course of disease. It mostly affects older adults in their sixth or seventh decade of life with male to female predominance of 3 to 1. It prognosis is very poor and the treatment is demanding. The golden standard therapy for younger, fit patients A 56- years old patient was admitted to the Department of Hematooncology and Bone Marrow Transplantation with clinical symptoms such as heavy night sweats, generalized enlargement of lymph nodes, massive weight loss, dyspnea and fatigue. Initial physical examination and imaging showed enormous hepatosplenomegaly, mass in the lungs and fluid in the pleural cavity.The patients underwent chemioimmunotherapy consolidated with an autologous stem cell transplant. To date, the patient is on maintenance treatment with ibrutinib.

Mantle cell lymphoma (MCL) is aggressive B-cell neoplasm diagnosed predominantly among older men. R-CHOP-like regimens allow to achieve high response rate, but the overall survival (OS) are disappointingly short - 3-4 years. An addition of high - dose cytarabine to the upfront therapy and autoSCT significantly improved outcomes but remain feasible largely for medically fit patients. Based on the activity and good tolerance of gemcitabine - oxaliplatin schemes in relapsed and refractory MCL patients, we developed an alternative first - line course for patients who are not eligible for R-HD-MTX-AraC. Aim. Assess toxicity and efficacy of R-DA-EPOCH/ R-HD-MTX-AraC and R-DA-EPOCH/R-GIDIOX schemes, autoSCT and R-maintenance in untreated MCL patients. Materials and methods. 47 untreated MCL patients from 6 centers were enrolled in prospective study between April 2008 and September 2013. All patients have stage II-V; ECOG 0-3; median age 55 years (29-64); Male/Female 76%/24%. MIPIb: 28% low, 33% intermediate and 39% high risk. Following 1st R-EPOCH patients were assigned to receive either R-DA-EPOCH/ R-HD-MTX-AraC or R-DA-EPOCH/ R-GIDIOX regimen. In the absence of renal failure, hematological toxicity grade 4 more than 3 days and severe infections patients received R-HD-MTX-AraC scheme (R 375 mg/m2 Day 0, Methotrexate 1000 mg/m2/24 hours Day 1, AraC 3000 mg/m2 q 12 hrs Days 2-3). Patients who had at least one of these complications received R-GIDIOX scheme (R 375 mg/m2 day 0, gemcitabine 800 mg/m2 days 1 and 4, ifosfamide 1000 mg/m2 days 1-5, dexamethasone 10 mg/m2 IV days 1-5, irinotecan 100 mg/m2 day 3, oxaliplatin 120 mg/m2 day 2). Subsequently these courses were alternating with R-DA-EPOCH in each arm of the protocol. Depending on the time of achieving CR patients received 6 or 8 courses, unless they progressed on therapy. Those patients who achieved PR/CR/CRu underwent autoSCT (BEAM-R). Post - transplant R-maintenance was administered for 3 years (R - 375 mg/m2 every 3 months). Results. 29/47 patients were treated on R-HD-MTX-AraC arm (median 50 years; MIPIb: 35.7% low, 28.6% intermediate, 35.7% high risk) and 18/47 patients were on R-GIDIOX arm (median 60 years; MIPIb: 16.7% low, 38.9% intermediate, 44.4% high risk). In R-HD-MTX-AraC arm CR rate was 96.5%. In R-GIDIOX arm OR and CR rates were 94.4% and 77.7% respectively. Main hematological toxicity of R-GIDIOX was leukopenia gr. 4 occurred in 74.1%. With median follow - up of 76 months, the estimated 7-years OS and EFS in R-HD-MTX-AraC arm are 76% and 57% respectively. In R-GIDIOX arm the estimated 7-years OS and EFS are 59% and 44%, respectively. There are no statistical differences in EFS (p=0.47) and OS (p=0.06) between two arms. Conclusions. The use of a risk - adapted strategy allowed 95.7% of patients achieve PR/CR/CRu, performed autoSCT and begun R-maintenance therapy with rituximab. None of the patients needed a premature discontinuation of therapy because of unacceptable toxicity. The performance of autoSCT and R-maintenance apparently allowed to partially offset differences in the intensity of induction therapy and to maintain comparable results of therapy in both induction arms.

Background: Mantle cell lymphoma (MCL) is a rare and clinically aggressive lymphoma subtype. Current approaches have greatly improved patients outcomes, but relapse is inevitable. In phase IIIII clinical trials, ibrutinib has shown significant activity in patients with relapsed or refractory (R/R) MCL., Aim: To assess efficacy and toxicity of ibrutinib monotherapy in patients with R/R MCL in routine practice outside of clinical trials., Materials and Methods: The study enrolled patients with confirmed R/R MCL who had received at least one line of previous chemotherapy. ECOG 24, cytopenia, infectious complications, hemorrhagic syndrome were not exclusion criteria. Patients received daily oral ibrutinib 560 mg until progression or unacceptable toxicity., Results: From May 2015 to September 2020 ibrutinib therapy was started in 106 patients with R/R MCL in 16 regions of Russia. The median age was 66 years; ECOG2 18%, blastoid variant (or Ki6740% or WBC50109/l) 43%. The median number of previous treatment lines was 2 (111). The ORR was 78.4% (CRR 27.4%). The median PFS was 13.6 months and OS 23.2 months. In the blastoid group the median PFS was 4.4 months vs 36.5 months in the alternative group (p0.001), the median OS 9.0 vs 41.0 (p=0.001). The median OS of patients after progression on ibrutinib was 3.2 months. The common complications are hemorrhages (63%), diarrhea (62%), myalgia and muscle cramps (60%), infections (31%), skin and nail toxicity 15%, arrhythmia 8%. None of recipients had to completely discontinue ibrutinib therapy due to complications., Conclusion: Ibrutinib is effective and well tolerated in routine practice of R/R MCL treatment and our results are consistent with international clinical trials. The favorable toxicity profile and the high response rate made it possible to prescribe ibrutinib in severe somatic status, cytopenia, and even in the presence of infectious complications.

The prevalence of multiple primary tumors has significantly increased last time. The question of choosing the optimal tactics of therapy today not fully resolved. Particular interest is the simultaneous detection of two neoplasms of similar origin in one study biopsy material. This publication presents a case of simultaneous diagnosis of myeloid sarcoma and mantle cell lymphoma in a 65-year-old patient, which required use of two different chemotherapy protocols. This example shows the need to use an extended diagnostic approach at all stages of the therapy, which allows choosing right tactics of therapy and achieving complete remission of two neoplasms.

Mantle cell lymphoma (MCL) is aggressive B-cell neoplasm diagnosed predominantly among older men. R-CHOP-like regimens allow to achieve high response rate, but the overall survival (OS) are disappointingly short - 3-4 years. An addition of high - dose cytarabine to the upfront therapy and autoSCT significantly improved outcomes but remain feasible largely for medically fit patients. Based on the activity and good tolerance of gemcitabine - oxaliplatin schemes in relapsed and refractory MCL patients, we developed an alternative first - line course for patients who are not eligible for R-HD-MTX-AraC., Aim: Assess toxicity and efficacy of R-DA-EPOCH/ R-HD-MTX-AraC and R-DA-EPOCH/R-GIDIOX schemes, autoSCT and R-maintenance in untreated MCL patients., Materials and Methods: 47 untreated MCL patients from 6 centers were enrolled in prospective study between April 2008 and September 2013. All patients have stage II-V; ECOG 0-3; median age 55 years (29-64); Male/Female 76%/24%. MIPIb: 28% low, 33% intermediate and 39% high risk. Following 1st R-EPOCH patients were assigned to receive either R-DA-EPOCH/ R-HD-MTX-AraC or R-DA-EPOCH/ R-GIDIOX regimen. In the absence of renal failure, hematological toxicity grade 4 more than 3 days and severe infections patients received R-HD-MTX-AraC scheme (R 375 mg/m2 Day 0, Methotrexate 1000 mg/m2/24 hours Day 1, AraC 3000 mg/m2 q 12 hrs Days 2-3). Patients who had at least one of these complications received R-GIDIOX scheme (R 375 mg/m2 day 0, gemcitabine 800 mg/m2 days 1 and 4, ifosfamide 1000 mg/m2 days 1-5, dexamethasone 10 mg/m2 IV days 1-5, irinotecan 100 mg/m2 day 3, oxaliplatin 120 mg/m2 day 2). Subsequently these courses were alternating with R-DA-EPOCH in each arm of the protocol. Depending on the time of achieving CR patients received 6 or 8 courses, unless they progressed on therapy. Those patients who achieved PR/CR/CRu underwent autoSCT (BEAM-R). Post - transplant R-maintenance was administered for 3 years (R - 375 mg/m2 every 3 months)., Results: 29/47 patients were treated on R-HD-MTX-AraC arm (median 50 years; MIPIb: 35.7% low, 28.6% intermediate, 35.7% high risk) and 18/47 patients were on R-GIDIOX arm (median 60 years; MIPIb: 16.7% low, 38.9% intermediate, 44.4% high risk). In R-HD-MTX-AraC arm CR rate was 96.5%. In R-GIDIOX arm OR and CR rates were 94.4% and 77.7% respectively. Main hematological toxicity of R-GIDIOX was leukopenia gr. 4 occurred in 74.1%. With median follow - up of 76 months, the estimated 7-years OS and EFS in R-HD-MTX-AraC arm are 76% and 57% respectively. In R-GIDIOX arm the estimated 7-years OS and EFS are 59% and 44%, respectively. There are no statistical differences in EFS (p=0.47) and OS (p=0.06) between two arms., Conclusions: The use of a risk - adapted strategy allowed 95.7% of patients achieve PR/CR/CRu, performed autoSCT and begun R-maintenance therapy with rituximab. None of the patients needed a premature discontinuation of therapy because of unacceptable toxicity. The performance of autoSCT and R-maintenance apparently allowed to partially offset differences in the intensity of induction therapy and to maintain comparable results of therapy in both induction arms.