Clinical Efficacy of Daratumumab in Monotherapy of Relapsed/Refractory Multiple Myeloma

SS Bessmeltsev1, EV Karyagina2, EYu Ilyushkina2, ZhL Stolypina2, RR Miftakhova1, II Kostroma1, TL Shelkovskaya2

1 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

2 Municipal Hospital No. 15, 4 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

For correspondence: Prof. Stanislav Semenovich Bessmeltsev, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-67-80, +7(911)228-18-01; e-mail: bsshem@hotmail.com, bessmeltsev@yandex.ru

For citation: Bessmeltsev SS, Karyagina EV, Ilyushkina EYu, et al. Clinical Efficacy of Daratumumab in Monotherapy of Relapsed/Refractory Multiple Myeloma. Clinical oncohematology. 2020;13(1):25–32. (In Russ).

DOI: 10.21320/2500-2139-2020-13-1-25-32


ABSTRACT

Background. Daratumumab is IgG1-κ humanized anti-CD38 monoclonal antibody. It has a direct impact on tumor and immunomodulatory effect.

Aim. To assess the efficacy of daratumumab monotherapy in patients with progressive, and relapsed/refractory multiple myeloma (MM), as well as to find out the degree of toxicity and safety of this drug.

Materials & Methods. The trial included 10 MM patients (3 men and 7 women) aged 51–74 years (median 57 years). Stage 3 (according to Durie-Salmon system) was determined in all patients, in 2 of them stage 3B with creatinine clearance < 30 mL/min was reported. According to ISS (International Staging System) criteria, stage 2 and stage 3 were identified in 6 and 4 patients, respectively. All the patients had been previously treated with bortezomib and lenalidomide with further double refractoriness in 4 out of 10 patients. Bendamustine and carfilzomib were administered to one patient each, both in combined regimens. The number of previous therapy lines was 3–6 (median 5).

Results. Overall response was 50 % including 2 (20 %) patients with very good partial remission. In 1 (10 %) patient complete remission was achieved. During the follow-up of 6–32 months (median 15 months) median overall survival was not achieved. Median progression-free survival was 17.8 months. Daratumumab is characterized by favorable safety profile. In 20 % of patients infusion-induced reactions with severity grades 1–2 were observed. Among other adverse events the following should be pointed out: weakness (30 %), nausea (10 %), headache (10 %), anorexia (10 %), thrombocytopenia (20 %), and neutropenia (30 %). No serious complications were reported.

Conclusion. Daratumumab treatment is a safe and effective method of anticancer drug therapy in relapsed/refractory MM.

Keywords: daratumumab, multiple myeloma, complete remission, overall response, survival, double refractoriness.

Received: August 22, 2019

Accepted: December 10, 2019

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    [Semochkin SV, Salogub GN, Bessmeltsev SS, Kaplanov KD. Practical Aspects of the Use of Carfilzomib in Multiple Myeloma. Clinical oncohematology. 2019;12(1):21–31. doi: 10.21320/2500-2139-2019-12-1-21-31. (In Russ)]

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Primary Bone Lymphomas: 18F-FDG PET and PET-CT as Methods of Diagnosis and Efficacy Estimation of Antitumor Treatment

AK Smol’yaninova1, ER Moskalets2, GA Yatsyk1, IE Kostina1, AS Bogolyubskaya3, NG Gabeeva1, EG Gemdzhian1, SA Tatarnikova1, DS Badmadzhapova1, EE Zvonkov1

1 National Research Center for Hematology, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

2 European Medical Center, 35 Shchepkina str., Moscow, Russian Federation, 129090

3 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova str., Moscow, Russian Federation, 117997

For correspondence: Anna Konstantinovna Smol’yaninova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; Tel.: +7(926)912-31-16; e-mail: annmo8@mail.ru

For citation: Smol’yaninova AK, Moskalets ER, Yatsyk GA, et al. Primary Bone Lymphomas: 18F-FDG PET and PET-CT as Methods of Diagnosis and Efficacy Estimation of Antitumor Treatment. Clinical oncohematology. 2020;13(1):33–49 (In Russ).

DOI: 10.21320/2500-2139-2020-13-1-33-49


ABSTRACT

Background. Primary bone lymphoma (PBL) is a rare malignant tumor. Initial examination aimed at detecting all primary lesions is an indispensable prerequisite for the choice of optimal antitumor treatment. Standard methods of diagnosis (X-ray, CT, and MRI) are not always adequate to measure the real tumor mass. Another well-known characteristic feature of PBL is a challenge in evaluating the effect of its treatment because of residual changes in the bones of most patients. However, the data on using 18F-FDG PET, another method of metabolic imaging, in PBL are rather rare in accessible literature.

Aim. To study the specific use of PET with 18F-FDG at initial examination and efficacy estimation of PBL treatment.

Materials & Methods. The trial included 21 PBL patients who received PET with 18F-FDG at initial examination and a month after the end of treatment. The results of 18F-FDG PET imaging were compared with the data obtained by means of structural diagnostic methods (CT and MRI) and the analysis of biopsy samples with pathologic lesions.

Results. Intensive uptake of 18F-FDG (SUVmax 8.6–40.1, mean SUVmax 23.5), according to PET data, was reported in all patients in those tumor lesions which were identified by the structural diagnostic methods and confirmed by biopsies. Besides, each of 21 cases showed pathologic infiltration of adjacent soft tissues with high metabolic activity. In PET-CT with 18F-FDG 13 further tumor localizations were revealed in 8 (38 %) patients. On completing the therapy, according to CT and MRI data, residual changes were observed in all (n = 21, 100 %) patients. The residual metabolic activity in the involved bones was identified in 13 (62 %) patients (SUVmax 2.91–8.7, mean SUVmax 4.2). In 4 of them the residual lesions were subjected to biopsy. None of 4 cases was reported to show tumors. Only in 1 out of 13 patients with residual metabolic changes a tumor relapse was detected. Overall 10-year survival in the groups of patients with and without FDG+ residual changes was 91 % and 100 %, respectively, with insignificant differences (= 0.39).

Conclusion. PET-CT with 18F-FDG is a highly sensitive technique for evaluating the primary lesion volumes in PBL patients. In 100 % of bone and soft tissue lesions an intensive uptake of 18F-FDG was observed. At the same time our study showed persistent metabolic activity on completing antitumor treatment in more than a half of patients, and in most of them it was not caused by tumor. Therefore, in our view, ongoing residual metabolic activity in PBL cannot always be regarded as an indication for continued treatment or consolidation radiotherapy.

Keywords: primary bone lymphoma, survival, positron emission tomography, diagnosis, efficacy estimation of antitumor treatment.

Received: August 2, 2019

Accepted: December 5, 2019

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Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues

KD Kaplanov1,2, NP Volkov1, TYu Klitochenko1, IV Matveeva1, AL Shipaeva1, MN Shirokova1, NV Davydova3, EG Gemdzhian4, DS Abramov5, DM Konovalov5, GL Snigur2, NA Red’kina1

1 Volgograd Regional Clinical Oncology Dispensary No. 1, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

2 Volgograd Medical Scientific Center, 1G Rokossovskogo str., Volgograd, Russian Federation, 400081

3 Consultation and Diagnosis Polyclinic No. 2, 114A Angarskaya str., Volgograd, Russian Federation, 400081

4 National Medical Hematology Research Center, 4а Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167

5 Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samory Mashela str., Moscow, Russian Federation, 117997

For correspondence: Kamil’ Daniyalovich Kaplanov, MD, PhD, 78 Zemlyachki str., Volgograd, Russian Federation, 400138; e-mail: kamilos@mail.ru

For citation: Kaplanov KD, Volkov NP, Klitochenko TYu, et al. Analysis Results of the Regional Registry of Patients with Diffuse Large B-cell Lymphoma: Risk Factors and Chemo-Immunotherapy Issues. Clinical oncohematology. 2019;12(2):154–64.

DOI: 10.21320/2500-2139-2019-12-2-154-164


ABSTRACT

Background & Aims. At least one third of patients with diffuse large B-cell lymphoma (DLBCL) are resistant to first-line therapy. R-CHOP chemo-immunotherapy does not yield acceptable results in high-risk patients. Effectiveness of options based either on increasing the dose intensity or on including auto-HSCT into the first-line therapy was not supported by the results of controlled studies. With this background the present study focuses on options, issues and failures of first-line on the basis of long-term follow-up of DLBCL patient population in the Volgograd Region.

Materials & Methods. From 2004 to 2017 the population-based registry of the Hematology Department in the Volgograd Regional Clinical Oncology Dispensary included all 492 primary DLBCL patients: 235 (48 %) men and 257 (52 %) women aged 18 to 88 years. Mean and median age was 59 and 61 years, respectively. CHOP therapy was administered to 206 (42 %) patients, and 223 (45 %) patients received R-CHOP. Other regimens including NHL-BFM-90 and R-DA-EPOCH were used only in 63 (13 %) patients. Second- and third-line therapies were administered to 145 (30 %) and 54 (11 %) patients, respectively. Value of the International Prognostic Index (IPI) and immunomorphologic characteristics was determined by multivariate Cox regression analysis. Pharmacoeconomic aspect of first-line therapy failures was analyzed using Markov model.

Results. Improvement of DLBCL therapy effects with the use of R-CHOP chemo-immunotherapy is particularly obvious in the groups with favorable and intermediate prognosis with 5-year overall survival (OS) of 90 % and 69 %, respectively. R-CHOP results are not considered to be satisfactory in the high-risk group: 5-year OS was 38 %. Pharmacoeconomic analysis proves the advantage of chemo-immunotherapy strategy in comparison with the period before rituximab era in terms of the life years gained (LYG) and the incremental cost-effectiveness ratio (ICER). With respect to immunotherapy effects the most significant immunomorphologic parameter is bcl-2 tumor cell expression. In the group of patients with bcl-2 > 50 % 5-year OS was 61 % with median of 88 months, event-free survival (EFS) was 52 % with median of 62 months. In the group without bcl-2 expression above the threshold 5-year OS and EFS were 88 % and 75 %, respectively, medians were not achieved. With c-myc and bcl-2 coexpression EFS and OS appeared to be even worse: 5-year EFS was 29 % with median of 6 months, and 5-year OS was 31 % with median of 15 months.

Conclusion. The analysis of actual practice demonstrates the need for new options of first-line therapy for DLBCL high-risk patients and also for introducing new discriminating prognostic factors which include the IPI-independent ones.

Keywords: diffuse large B-cell lymphoma, R-CHOP, chemoimmunotherapy, survival, pharmacoeconomics, Markov model, life years gained (LYG), incremental cost-effectiveness ratio (ICER).

Received: July 16, 2018

Accepted: January 10, 2019

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Clinical Efficacy of Chelation Therapy in Patients with Low-Risk Myelodysplastic Syndrome

SV Gritsaev, II Kostroma, AA Zhernyakova

Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Sergei Vasil’evich Gritsaev, MD, PhD, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-54-68; e-mail: gritsaevsv@mail.ru

For citation: Gritsaev SV, Kostroma II, Zhernyakova AA. Clinical Efficacy of Chelation Therapy in Patients with Low-Risk Myelodysplastic Syndrome. Clinical oncohematology. 2019;12(2):120–4.

DOI: 10.21320/2500-2139-2019-12-2-120-124


ABSTRACT

The present literature review provides evidence that in patients with low-risk myelodysplastic syndrome and transfusion dependence blood parameters and survival rates can be improved by administration of iron chelators. Dose adequacy and therapy duration underlie clinical efficacy of chelators. Toxicity can be reduced by administrating a new formula of deferasirox that does not need to be dissolved in liquid before consuming.

Keywords: myelodysplastic syndrome, low risk, transfusion dependence, iron chelators, survival.

Received: August 20, 2018

Accepted: February 2, 2019

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Epidemiology of Multiple Myeloma in Novosibirsk (Siberian Federal District)

NV Skvortsova1, TI Pospelova1, IB Kovynev1, GS Soldatova2, IN Nechunaeva3

1 Novosibirsk State Medical University, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091

2 Novosibirsk National Research State University, 2 Pirogova str., Novosibirsk, Russian Federation, 630090

3 Municipal Clinical Hospital No. 2 of Novosibirsk Region, Center of Hematology, 21 Polzunov str., Novosibirsk, Russian Federation, 630051

For correspondence: Nataliya Valer’evna Skvortsova, MD, PhD, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091; Tel.: +7(905)955-59-91; e-mail: nata_sk78@mail.ru.

For citation: Skvortsova NV, Pospelova TI, Kovynev IB, et al. Epidemiology of Multiple Myeloma in Novosibirsk (Siberian Federal District). Clinical oncohematology. 2019;12(1):86–94.

DOI: 10.21320/2500-2139-2019-12-1-86-94


ABSTRACT

Aim. To analyze major epidemiological parameters of multiple myeloma, i.e. registered incidence, prevalence, mortality, and survival in Novosibirsk, megalopolis in Siberian Federal District.

Materials & Methods. The study covered medical records of 335 patients with newly diagnosed multiple myeloma (MM) treated from January 1, 2006 to December 31, 2016 at the Center of Hematology in Novosibirsk. Median age was 67 years (range 30–89), the trial enrolled 218 (65 %) women and 117 (35 %) men.

Results. Over the last decade the mean registered MM incidence in Novosibirsk increased by 1.6 times, and MM prevalence increased by 4.9 times. These parameters correspond to 2.4 and 13.8 per 100,000 population per year, respectively, with the linear trend of growth which demonstrates not only the increased number of patients with newly diagnosed MM, but the increased longevity of them. MM incidence and prevalence parameters are significantly higher in women than in men, which most probably can be accounted for by specific administrative factors in the Novosibirsk region. Yearly mortality of MM patients decreased from 28.3 % to 8.2 % with a negative linear trend over the entire analyzed period, which is most likely to be associated with availability of new drugs and transplantation procedures.

Conclusion. The obtained epidemiological data will enable to plan the provision of timely and effective care for MM patients and to elaborate a system of judicious allocation of costly equipment and drugs.

Keywords: multiple myeloma, epidemiology, registered incidence, prevalence, mortality, survival.

Received: September 24, 2018

Accepted: December 27, 2018

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Clinical and Hematological Predictors of Response to First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma

SV Samarina1, EL Nazarova1, NV Minaeva1, EN Zotina1, IV Paramonov1, SV Gritsaev2

1 Kirov Research Institute of Hematology and Transfusiology, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027

2 Russian Research Institute of Hematology and Transfusiology, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

For correspondence: Svetlana Valer’evna Samarina, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; e-mail: samarinasv2010@mail.ru

For citation: Samarina SV, Nazarova EL, Minaeva NV, et al. Clinical and Hematological Predictors of Response to First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019;12(1):68–72.

DOI: 10.21320/2500-2139-2019-12-1-68-72


ABSTRACT

Aim. To assess the prognostic value of clinical and hematological parameters used by hematologists for risk stratification in diffuse large B-cell lymphoma (DLBCL), and to justify the need for discovering new prognostic factors.

Methods. The trial included 101 patients (48 men and 53 women) with newly diagnosed DLBCL at the age of 18–80 years (median age 58 years). The patients received R-CHOP as first-line therapy. Depending on their response all patients were stratified into 4 groups: with complete response (CR; n = 58), partial response (PR; n = 15), resistance to first-line therapy (n = 19), and early relapses (ER; n = 9). Median follow-up was 22 months (range 2–120 months).

Results. In terms of age influence on the efficacy of R-СНОР as first-line therapy no significant differences were established in regard to response in patients younger and older than 65 years. Statistically significant differences were observed while analyzing two parameters of International Prognostic Index (IPI; disease stage and extranodal lesions) and B-symptoms in the CR and therapy-resistant groups. With respect to the same parameters no significant differences were found in the CR and ER groups. Median 2-year disease-free survival was not achieved in patients with CR. In patients with PR it was 12 months. Median 2-year overall survival in patients with CR, PR, and ER was not achieved, and in patients with therapy-resistant DLBCL it was 10 months.

Conclusion. Results of the trial confirm prognostic value of factors applied for risk stratification in DLBCL. However, variability of clinical course of the disease, especially with a low IPI score, suggests the need for new prognostic parameters associated with the course of DLBCL.

Keywords: diffuse large B-cell lymphoma, prognosis, induction therapy, survival.

Received: June 5, 2018

Accepted: December 3, 2018

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REFERENCES

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Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region

VI Bakhtina1,2, IV Demko2, AN Narkevich2, DS Gushchin3

1 Regional Clinical Hospital, 3а Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

2 Professor VF Voyno-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

3 Norilsk Inter-District Hospital No. 1, Solnechnyi pr-d, 7a Norilsk, Russian Federation, 663300

For correspondence: Varvara Ivanovna Bakhtina, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022; Tel: +7(923)357-57-77; е-mail: doctor.gem@mail.ru

For citation: Bakhtina VI, Demko IV, Narkevich AN, Gushchin DS. Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region. Clinical oncohematology. 2016;9(4):413–419 (In Russ).

DOI: 10.21320/2500-2139-2016-9-4-413-419


ABSTRACT

Background & Aims. B-cellular chronic lymphocytic leukemia (CLL) is a disease with heterogeneous clinical manifestations and biological characteristics. The age of 70 % of patients is more than 65 years by the date of the diagnosis; most of them have several comorbidities. The aim of the study is to identify factors affecting the survival, as well as to determine causes of mortality in CLL patients (according to data from hematological hospitals of Krasnoyarsk Region).

Methods. In order to identify the most significant factors affecting the course and the outcome of CLL, a retrospective analysis of data on patients who died in hematological hospitals was carried out. 45 cases with the lethal outcome were registered within six years. All patients were under hematologist’s supervision after diagnosing the disease, and they were followed throughout the treatment period up to the lethal outcome.

Results. Тhe overall and progression-free survival depended, first of all, on the type of the first line therapy and its efficacy. The progression of the underlying disease and infectious complications became the main reason of the lethal outcome in CLL patients.

Conclusion. Most patients received ineffective treatment as first line therapy. The analysis of the comorbidities showed that a more effective chemotherapy could be performed with achievement of longer complete remissions.


Keywords: chronic lymphocytic leukemia, oncohematological diseases, comorbidities, survival, treatment.

Received: May 16, 2016

Accepted: June 17, 2016

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REFERENCES

  1. Gribben JG. How I treat CLL up front. Blood. 2010;115(2):187– doi: 10.1182/blood-2009-08-207126.
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Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region

VI Bakhtina1,2, IV Demko2, AN Narkevich2, DS Gushchin3

1 Regional Clinical Hospital, 3а Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

2 Professor VF Voyno-Yasenetsky Krasnoyarsk State Medical University, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022

3 Norilsk Inter-District Hospital No. 1, Solnechnyi pr-d, 7a Norilsk, Russian Federation, 663300

For correspondence: Varvara Ivanovna Bakhtina, 1 Partizana Zheleznyaka Str., Krasnoyarsk, Russian Federation, 660022; Tel: +7(923)357-57-77; е-mail: doctor.gem@mail.ru

For citation: Bakhtina VI, Demko IV, Narkevich AN, Gushchin DS. Factors Affecting Course and Outcome of Chronic Lymphocytic Leukemia: Data from Hematological Hospitals of Krasnoyarsk Region. Clinical oncohematology. 2016;9(4):413–419 (In Russ).

DOI: http://dx.doi.org/10.21320/2500-2139-2016-9-4-413-419


ABSTRACT

Background & Aims. B-cellular chronic lymphocytic leukemia (CLL) is a disease with heterogeneous clinical manifestations and biological characteristics. The age of 70 % of patients is more than 65 years by the date of the diagnosis; most of them have several comorbidities. The aim of the study is to identify factors affecting the survival, as well as to determine causes of mortality in CLL patients (according to data from hematological hospitals of Krasnoyarsk Region).

Methods. In order to identify the most significant factors affecting the course and the outcome of CLL, a retrospective analysis of data on patients who died in hematological hospitals was carried out. 45 cases with the lethal outcome were registered within six years. All patients were under hematologist’s supervision after diagnosing the disease, and they were followed throughout the treatment period up to the lethal outcome.

Results. Тhe overall and progression-free survival depended, first of all, on the type of the first line therapy and its efficacy. The progression of the underlying disease and infectious complications became the main reason of the lethal outcome in CLL patients.

Conclusion. Most patients received ineffective treatment as first line therapy. The analysis of the comorbidities showed that a more effective chemotherapy could be performed with achievement of longer complete remissions.

Keywords: chronic lymphocytic leukemia, oncohematological diseases, comorbidities, survival, treatment.

Received: May 16, 2016

Accepted: June 17, 2016

Read in PDF (RUS) pdficon

REFERENCES

  1. Gribben JG. How I treat CLL up front. Blood. 2010;115(2):187– doi: 10.1182/blood-2009-08-207126.
  2. Lee JS, Dixon DO, Kantarjian H, et al. Prognosis of chronic lymphocytic leukemia: a multivariate regression analysis of 325 untreated patients. Blood. 1987;69(3):929–36.
  3. Molica S. Infections in chronic lymphocytic leukemia: risks factors and impact on survival and treatment. Leuk Lymphoma. 1994;13(3–4):203–14. doi: 10.3109/10428199409056283.
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