overall survival

Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA ,

EV Vaneeva, VA Rosin, DA Dyakonov, SV Samarina, IV Paramonov

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

For correspondence: Elena Viktorovna Vaneeva, 72 Krasnoarmeiskaya ul., Kirov, Russian Federation, 610027; Tel.: +7(922)975-23-34; e-mail: vaneeva.elena.vic@mail.ru

For citation: Vaneeva EV, Rosin VA, Dyakonov DA, et al. Significance of the Expression of pAKT1 and pSyk Activation Proteins in Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2022;15(2):140–7. (In Russ).

DOI: 10.21320/2500-2139-2022-15-2-140-147

ABSTRACT

Aim. To assess the prognostic value of pAKT1 and рSyk expression in DLBCL.

Materials & Methods. The study enrolled 100 patients with newly diagnosed DLBCL treated with R-CHOP first-line immunochemotherapy. The relative count of pAKT1- and pSyk-expressing tumor cells was determined by immunohistochemical and morphometric methods. The expression cut-off of these proteins was calculated by ROC analysis. The relationship of protein expression with clinical parameters of DLBCL was analyzed by Fisher’s exact two-tailed test. The 5-year overall (OS) and progression-free (PFS) survivals were estimated by Kaplan-Meier method (log-rank test).

Results. High pAKT1 expression was associated with advanced DLBCL stages, International Prognostic Index > 2, serum lactate dehydrogenase concentration above normal, failures of R-CHOP therapy, as well as worse OS and PFS. No correlation between рSyk expression and clinical lymphoma characteristics was found. The worst 5-year OS (27.6 %) was reported in cases of pAKT1 and pSyk co-overexpression (hazard ratio [HR] 5.2; 95% confidence interval [95% CI] 2.49–10.9; p < 0.001). A similar trend was observed for PFS (HR = 3.3; 95% CI 1.54–7.30; p = 0.002).

Conclusion. Overexpression of pAKT1 is an informative indicator of a poor DLBCL prognosis. Co-overexpression of pAKT1 and рSyk markers is associated with worse OS and PFS compared to their isolated expressions and other co-expression variants.

Keywords: diffuse large B-cell lymphoma, pAKT1 and pSyk expression, overall survival, progression-free survival.

Received: November 17, 2021

Accepted: March 2, 2022

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REFERENCES

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A Rationale for a New Operational Integrated Quality and Efficiency Index for Assessing the Performance of Hematological Services in Constituent Entities of the Russian Federation

AUTOIMMUNE THROMBOCYTOPENIA , ,

EN Parovichnikova1, TTs Garmaeva1, OV Lazareva1, KA Lukina1, YuA Chabaeva1, SM Kulikov1, VV Troitskaya1, TV Gaponova1, LI Menshikova2, VG Savchenko1

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

2 Federal Research Institute for Health Organization and Informatics, 11 Dobrolyubova str., Moscow, Russian Federation, 127254

For correspondence: Elena Nikolaevna Parovichnikova, MD, PhD, 4 Novyi Zykovskii pr-d, Moscow, Russian Federation, 125167; e-mail: parovichnikova@gmail.com

For citation: Parovichnikova EN, Garmaeva TTs, Lazareva OV, et al. A Rationale for a New Operational Integrated Quality and Efficiency Index for Assessing the Performance of Hematological Services in Constituent Entities of the Russian Federation. Clinical oncohematology. 2022;15(1):1–15. (In Russ).

DOI: 10.21320/2500-2139-2022-15-1-1-15

ABSTRACT

Background. Since 2018 a widespread national project “Healthcare” has been implemented in the Russian Federation (RF) to improve the quality, efficiency, availability, and affordability of medical care in the profiles of specialties in constituent entities of the RF. Modern hematology as a medical field of high technology and crucial solutions is notable for its multi- and interdisciplinarity of most nosological forms, complexity of diagnostic process, multi-structuredness and diversity of related physician teams in different structural units and subdivisions. One of the key issues in federal projects is to determine the indicators for assessing the efficiency of regional hematological services in constituent entities of the RF.

Aim. To elaborate and substantiate a new integrated operational efficiency index for hematological services in constituent entities of the RF.

Materials & Methods. The analysis of data and assessment of feasibility of a new integrated operational index “early mortality in acute leukemia” (AL) were based on the results of 5 multi-center trials, including an epidemiological one.

Results. Multi-center clinical studies on AL are the only objective tools for assessing the treatment efficacy, its improvement, and further training of hematologists taking part in the trials. AL treatment requires well-developed infrastructure of hematological services involving not only staff matters and organization of hematologists’ activities, but also management of many highly important related subdivisions and laboratories, logistics of their interaction, time specifications, meeting clinical guidelines, and lastly, and most importantly, financial support.

Conclusion. The Unified State Information System “Hematology” is the only platform providing the objective information on patients’ vital status and enabling the use of the suggested integrated index for assessing the quality and efficiency of hematological services in the regions of the RF. This indicator of early mortality in AL patients less than 60 years of age is 15 % for acute myeloid leukemias and 10 % for acute lymphoblastic leukemias. Its low values would demonstrate that this or that constituent entity of the RF is provided with sufficient infrastructure, technologies, and a professional team to keep those patients alive who have severe but curable hematological diseases. The indicator of long-term survival or “life years gained” should become the main strategic criterion for the therapy efficacy in hematological diseases.

Keywords: hematological services, assessment of the medical care quality, early mortality, overall survival, acute leukemia, acute myeloid leukemia, acute lymphoblastic leukemia.

Received: September 27, 2021

Accepted: December 15, 2021

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Value of PD-L1 Protein Expression in the Combined Prognostic Model of Diffuse Large B-Cell Lymphoma

AUTOIMMUNE THROMBOCYTOPENIA ,

SV Samarina1, NYu Semenova2, NV Minaeva1, DA Dyakonov1, VA Rosin1, EV Vaneeva1, 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 Valerevna Samarina, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(8332)25-46-88; e-mail: samarinasv2010@mail.ru

For citation: Samarina SV, Semenova NYu, Minaeva NV, et al. Value of PD-L1 Protein Expression in the Combined Prognostic Model of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2021;14(3):308–14. (In Russ).

DOI: 10.21320/2500-2139-2021-14-3-308-314

ABSTRACT

Aim. To study the value of PD-L1 protein expression in the combined model of diffuse large B-cell lymphoma (DLBCL) after administration of R-СHOP induction immunochemotherapy.

Materials & Methods. A retrospective analysis was based on the data of 85 DLBCL patients. The median age was 59 years (Q1–Q3: 29–83). Each patient received at least 2–6 courses of R-СHOP immunochemotherapy. The median follow-up period was 17 months. The optimal cut-off threshold for assessing the proportion of tumor cells expressing PD-L1 protein was determined by the САRT (Classification and Regression Tree) method.

Results. Patients were divided into three groups depending on IPI (International Prognostic Index) risk and immunohistochemical subtype (Hans algorithm) using CART. In group 1 with immunohistochemical GCB subtype and any IPI risk, except for the high one, low PD-L1 expression measured in terms of the DLBCL expressing tumor cell count, was identified in 21 (84 %) patients, 4 (16 %) patients showed overexpression. In case of low PD-L1 expression the 2-year progression-free survival (PFS) was 76 % (median not reached). In 4 patients with protein overexpression, the life duration after DLBCL diagnosed was 4, 16, 2, and 6 months, respectively. In group 2 with immunohistochemical non-GCB subtype and any IPI risk, except for the high one, 27 (67.5 %) patients showed low, and 13 (32.5 %) patients showed high PD-L1 expression. The analysis of the 2-year PFS resulted in no significant differences in groups with different relative counts of РD-L1 expressing tumor cells, i.e., 46 % and 49 %, respectively (p = 0.803). In case of low (< 24.5 % tumor cells) PD-L1 expression, the 2-year overall survival (OS) was better than in patients with overexpression (≥ 24.5 % tumor cells), i.e., 87 % vs. 52 %, respectively (p = 0.049). In group 3 with IPI high risk irrespective of immunohistochemical subtype, the proportion of PD-L1 expressing cells was higher than cut-off threshold (≥ 24.5 %) in 9 (45 %) patients, low protein expression was identified in 11 (55 %) patients. Deaths were reported in all patients of group 3 showing PD-L1 overexpression. In case of low protein expression the proportion of patients alive was 46 % (p = 0.002). None of the patients with high PD-L1 expression lived longer than 2 years. In those with low PD-L1 expression the 2-year OS was 66 % (p = 0.008).

Conclusion. Overexpression of PD-L1 by DLBCL tumor cells together with high IPI progression risk and non-GCB tumor subtype is associated with the worst OS and PFS. It can probably be accounted for by insufficient efficacy of R-СHOP induction immunochemotherapy in patients with high IPI risk. With this presumption, the PD-L1 expressing tumor cell count can be regarded as an important additional criterion for stratification of DLBCL patients into risk groups. Adding this new parameter to already established ones would probably contribute to differentiated approach to the choice of chemotherapy strategy at the onset of this aggressive lymphoma.

Keywords: diffuse large B-cell lymphoma, PD-L1 expression, overall survival, progression-free survival.

Received: January 29, 2021

Accepted: May 15, 2021

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Статистика Plumx английский

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Comorbidity and Personalized Treatment of Multiple Myeloma in Real Clinical Practice

AUTOIMMUNE THROMBOCYTOPENIA , ,

NV Skvortsova1, IB Kovynev1, KV Khalzov1, TI Pospelova1, IN Nechunaeva2

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

2 Municipal Clinical Hospital No. 2, 21 Polzunova str., Novosibirsk, Russian Federation, 630051

For correspondence: Nataliya Valer’evna Skvortsova, MD, PhD, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091; Tel.: 8(905)955-59-91; Fax: 8(383)279-94-06; e-mail: nata_sk78@mail.ru

For citation: Skvortsova NV, Kovynev IB, Khalzov KV, et al. Comorbidity and Personalized Treatment of Multiple Myeloma in Real Clinical Practice. Clinical oncohematology. 2020;13(3):322–34 (In Russ).

DOI: 10.21320/2500-2139-2020-13-3-322-334

ABSTRACT

Aim. To study incidence and structure of comorbidity in multiple myeloma (MM) patients depending on their age; to determine its effect on overall survival, efficacy, and safety of the first-line therapy in real clinical practice.

Materials & Methods. Overall, 369 patients with newly diagnosed MM were enrolled in the trial from January 2012 to December 2017. Among them there were 134 men and 235 women hospitalized at the Unit of Hematology in the Novosibirsk Municipal Clinical Hospital No. 2. Median age of patients was 67 years (range 32–82 years).

Results. The analyzed patients were divided into three age groups: the first group of young/middle age (32–59 years) (n = 105), the second group of elderly patients (60–74 years) (n = 186), and the third group of old age (≥ 75 years) (n = 78). In each patient prior to chemotherapy the comorbidity spectrum was identified and CIRS-G, CCI, and MCI comorbidity scores were calculated. Patients with newly diagnosed MM in real clinical practice prove to have high and increasing with age comorbidity incidence (91 % in patients of young/middle age, 97,7 % and 100 % in patients of elderly and old age, respectively). Comorbidity significantly reduces overall survival (OS) of MM patients. Important OS predictors are rhythm and conduction disorder (odds ratio, OR, 2.762; p < 0.002), chronic pancreatitis (OR 1.864; p < 0.001), exogenous constitutive obesity (OR 1.948; p < 0.002), chronic obstructive pulmonary disease (OR 2.105; p < 0.021), chronic kidney disease, stage С4–С5 (OR 2.255; p < 0.003), and chronic heart failure, functional class II (OR 1.915; p < 0.002). Highest importance in predicting OS, efficacy, and tolerance to chemotherapy in MM patients is attached to MCI score (OR 3.771; p < 0.001). MM patients with high risk by MCI are characterized by lower rate and depth of response to the first-line therapy, shorter time before the first relapse, higher incidence of non-hematologic toxicity of grade ≥ 3, and therapy withdrawal or drug dose reduction.

Conclusion. Comorbidity assessment in MM patients is important for outcome prediction and treatment planning.

Keywords: multiple myeloma, comorbidity, comorbidity scores, overall survival, personalized treatment.

Received: April 2, 2020

Accepted: June 18, 2020

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Immunohistochemical Subtype and Parameters of International Prognostic Index in the New Prognostic Model of Diffuse Large B-Cell Lymphoma

LYMPHOID TUMORS , , , ,

SV Samarina1, AS Luchinin1, NV Minaeva1, IV Paramonov1, DA D’yakonov1, EV Vaneeva1, VA Rosin1, 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; Tel.: +7(912)732-47-56; e-mail: samarinasv2010@mail.ru

For citation: Samarina SV, Luchinin AS, Minaeva NV, et al. Immunohistochemical Subtype and Parameters of International Prognostic Index in the New Prognostic Model of Diffuse Large B-Cell Lymphoma. Clinical oncohematology. 2019;12(4):385–90 (In Russ).

DOI: 10.21320/2500-2139-2019-12-4-385-390

ABSTRACT

Aim. To develop an integrated prognostic model of diffuse large B-cell lymphoma (DLBCL) on the basis of immunohistochemical tumor subtype and parameters of International Prognostic Index (IPI).

Materials & Methods. Out of 104 DLBCL patients in the data base 81 (77.9 %) met the eligibility criteria. Median age was 58 years (range 23–83). All patients were treated with R-СНОР. The creation of overall survival (OS) prognostic model for DLBCL patients was based on machine learning with classification and regression trees. OS was analyzed using Kaplan-Meier method. Survival curves were compared by means of log rank test and hazard ratio (HR). Any test was considered significant if two-sided level of p < 0.05 was reached.

Results. Following the developed model three groups of patients were identified: the 1st group of low risk (the combination of low, intermediate-low, and intermediate-high risks according to IPI and GCB subtype); the 2nd group of intermediate risk (the combination of low, intermediate-low, and intermediate-high risks according to IPI and non-GCB subtype); the 3d group of high risk (irrespective of subtype). In the group of low risk (n = 26) 2-year OS during the monitoring period was 100 %. In the group of intermediate risk (n = 34) median OS was not reached, 2-year OS was 74 %, and expected 5-year OS was 68 %. In the group of high risk (n = 21) median OS was 25 months, 2-year OS was 46 %, and expected 5-year OS was 37 % (log rank p < 0.0001). HR calculated for the high-risk group compared with the low- and intermediate-risk groups was 5.1 (95% CI 2.1–12.1; p = 0.0003).

Conclusion. A new integrated system of DLBCL prognosis is suggested which includes IPI risk parameters and immunohistochemical subtype based on Hans algorithm. This prognostic system can be used in clinical practice for DLBCL patient stratification and risk-adapted therapy.

Keywords: diffuse large B-cell lymphoma, overall survival, prognosis, International Prognostic Index, machine learning.

Received: March 18, 2019

Accepted: August 27, 2019

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REFERENCES

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Evolution of Anti-Cancer Treatment and its Impact on Surrogate Prognostic Factors in Multiple Myeloma

LYMPHOID TUMORS , , ,

AS Luchinin1, SV Semochkin2, NV Minaeva1, NM Pozdeev1, IV Paramonov1

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

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

For correspondence: Aleksandr Sergeevich Luchinin, 72 Krasnoarmeiskaya str., Kirov, Russian Federation, 610027; Tel.: +7(919)506-87-86; e-mail: glivec@mail.ru

For citation: Luchinin AS, Semochkin SV, Minaeva NV, et al. Evolution of Anti-Cancer Treatment and its Impact on Surrogate Prognostic Factors in Multiple Myeloma. Clinical oncohematology. 2018;11(2):175–81.

DOI: 10.21320/2500-2139-2018-11-2-175-181

ABSTRACT

Aim. To assess prognostic value of surrogate clinical and laboratory markers in current therapy of multiple myeloma (MM).

Materials & Methods. The analysis included 567 patients (215 men and 352 women), the Kirov region inhabitants with newly diagnosed MM over the period from January 1, 1994 to December 31, 2016. The median age was 64 years (range 29–90). Patients were divided into two groups: the first group received treatment from 1994 to 2005 (n = 269), the second group received treatment from 2006 to 2016 (n = 298). Impact of factors on overall survival (OS) was evaluated by multivariate logistic regression analysis using the Cox method.

Results. Over the period from 2006 to 2016 the number of patients treated with traditional chemotherapy decreased from 78.4 to 32.5 %. At the same time the number of patients treated with bortezomib-based regimens increased from 1.9 to 56.3 % and autologous hematopoietic stem cell transplantation (auto-HSCT) protocols — from 1.4 to 14.0 %. Median OS over the period from 1994 to 2005 was 27 months. It increased to 55 months in the period of 2006–2016. In the reference decades 5-year overall survival increased from 21 % (95% confidence interval [95% CI] 17–27 %) to 47 % (95% CI 39–55 %), respectively (hazard ratio [HR] 0.51; 95% CI 0.41–0.64; p < 0,0001). In patients treated with bortezomib-based regimens over the period from 2006 to 2016 median OS increased to 73 months compared to 27 months in 1994–2005. In patients aged ≤ 65 years and treated with auto-HSCT median OS was not reached, and median OS in patients without auto-HSCT treatment was 54 months.

Conclusions. Surrogate prognostic markers, such as the age over 65, hemoglobin level < 100 g/L, β2-microglobulin ≥ 6 mg/L, serum creatinine ≥ 177 µmol/L and stage III according to ISS and Durie-Salmon, are unfavourable predictors of survival of MM patients.

Keywords: multiple myeloma, prognosis, bortezomib, auto-HSCT, overall survival.

Received: December 21, 2017

Accepted: February 25, 2018

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Hematological Improvement is a Favorable Response to Azacitidine in Patients with Acute Myeloid Leukemias and Myelodysplastic Syndromes

MYELOID TUMORS , , , ,

I.I. Kostroma1, S.V. Gritsaev1, E.V. Karyagina2, A.S. Nizamutdinova3, I.S. Martynkevich1, K.M. Abdulkadyrov1

1 Russian Scientific Research Institute of Hematology and Transfusiology under the Federal Medico-Biological Agency, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024

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

3 Alexandrovskaya Municipal Hospital No. 17, 4 pr-t Solidarnosti, Saint Petersburg, Russian Federation, 193312

For correspondence: Ivan Ivanovich Kostroma, 16 2-ya Sovetskaya str., Saint Petersburg, Russian Federation, 191024; Tel.: +7(812)717-58-57; e-mail: obex@rambler.ru

For citation: Kostroma II, Gritsaev SV, Karyagina EV, et al. Hematological Improvement is a Favorable Response to Azacitidine in Patients with Acute Myeloid Leukemias and Myelodysplastic Syndromes. Clinical oncohematology. 2015;8(4):413–419 (In Russ).

DOI: 10.21320/2500-2139-2015-8-4-413-419

ABSTRACT

Aim. To evaluate types of response to azacitidine associated with improvement of overall survival (OS) rates of patients with acute myeloid leukemias (AML) and myelodysplastic syndromes (MDS).

Methods. A retrospective analyses of medical records of 14 AML patients and 13 MDS patients at the age of 39 to 84 treated with azacitidine at a dose of 75 mg/m2 subcutaneously for 7 subsequent days every 28 days was performed. The therapy effectiveness was evaluated according to modified 2006 IWG criteria. The OS was calculated beginning with the date of initiation of the azacitidine therapy.

Results. From 2 to 25 azacitidine cycles was performed. Complete remission (CR) was achieved in 6 patients (22.2 %) including 4 AML and 2 MDS patients. Bone marrow remission (mCR) was diagnosed in 1 MDS patient (3.7 %). Hematological improvement was obtained in 11 patients (40.7 %) including 5 AML and 6 MDS patients. The overall response was 66.7 % (18 to 27 patients). There was no correlation between the therapy effectiveness and patients’ age, disease type, duration of the previous period, baseline hemoglobin, leukocytes, and platelets levels, and dependence on transfusions of erythrocyte suspension and thromboconcentrate. The therapy was considered ineffective in 9 patients (33.3 %). Stabilization with retained requirements of blood component transfusion was observed in 4 AML and 3 MDS patients. 2 patients presented gradual increase of the blast cell count in the bone marrow. The follow-up period was 2–29 months. The median OS of all patients was 11.5 months. The median OS of patients with CR, mCR and hematological improvement was significantly greater than that in the group of patients with stable disease and progression: 15.9 versus 7.4 months, respectively (p = 0,010).

Conclusion. Reduction of transfusion requirement and/or stable improvement of peripheral blood levels due to azacitidine administration are associated with improved OS rates of AML and MDS patients.

Keywords: acute myeloid leukemia, myelodysplastic syndromes, azacitidine, hematological improvement, overall survival.

Received: April 6, 2015

Accepted: October 22, 2015

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Multiple Myeloma: 7-Year Experience of Applying Targeted Therapy in Novosibirsk and Its Results

LYMPHOID TUMORS , ,

T.I. Pospelova1, N.V. Skvortsova1, I.N. Nechunaeva2

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

2 Municipal Hospital No. 2, 21 Polzunova str., Novosibirsk, Russian Federation, 630051

For correspondence: Nataliya Valer’evna Skvortsova, PhD, associate professor, 52 Krasnyi pr-t, Novosibirsk, Russian Federation, 630091; Tel.: +8(383)279-94-06; e-mail: nata_sk78@mail.ru

For citation: Pospelova T.I., Skvortsova N.V., Nechunaeva I.N. Multiple Myeloma: 7-Year Experience of Applying Targeted Therapy in Novosibirsk and Its Results. Klin. Onkogematol. 2015;8(3):267–73. (In Russ.)

ABSTRACT

Objective. To evaluate results of the 7-year experience in treatment of multiple myeloma (MM) with proteasome inhibitor (bortezomib) in the Novosibirsk Municipal Hematological Center.

Methods. 199 MM patients treated in the Novosibirsk Municipal Hematological Center over the period from July, 2006, till December, 2014, were enrolled in the study. The median age of patients was 68 years (varied from 36 to 81). 98 patients received bortezomib as the first line therapy and 101 patients as the second line.

Results. The overall response rate of the first line therapy was 78.5 %; at that, 25 % of patients achieved a complete and almost complete remission. The median time to achieve response was 72 days. With the progression or refractory MM, the efficacy of bortezomib as a part of a combined antitumor therapy was 68.3 %. Bortezomib proved to be effective when its administration was resumed by patients who had received bortezomib and other components of the combined regimen previously (overall response: 68.4 %). The median overall survival rate has not been achieved, and 7-year survival rate was 70 %. Adverse events of bortezomib were predictable and manageable; the most relevant of them included gastrointestinal and hematologic disorders, fatigue, and peripheral neuropathy.

Conclusion. Bortezomib is a highly effective drug, which plays an important role in the treatment of MM as the first and subsequent line therapies; its administration results in significant increase in patients’ overall survival.

Keywords: multiple myeloma, effectiveness of treatment, bortezomib, overall survival.

Received: February 16, 2015

Accepted: May 28, 2015

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Management of relapsed and refractory multiple myeloma: literature review and our data. Part III

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , , , , , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

Abstract

Advances in treatment options for patients with multiple myeloma have made a significant impact on overall survival and have helped to achieve the rates of response and duration of remission previously not unachievable with standard chemotherapy-based approaches. These improvements are due, in a large part, to the development of the novel agents, including bortezomib, thalidomide, and lenalidomide, each of which has substantial single-agent activity. Combinations of bortezomib, thalidomide, and lenalidomide with conventional agents or among each other have resulted in enhanced response rates and efficacy. However, when patients are unresponsive to immunomodulatory drugs and bortezomib, the prognosis becomes poor. A number of novel agents are being tested in multiple myeloma, but relapsed/refractory multiple myeloma still represents a challenge and difficult area for drug development. Therefore, the new agents are needed. In addition, a large number of second- or third-generation agents are also in clinical development, such that the repertoire of available treatment options continues to expand. Such agents as carfilzomib, pomalidomide, vorinostat, panobinistat, romidepsin, perifosine, tanespimycin, bendamustine, and elotuzumab are just a few out of many exciting new compounds that are being tested in phases I, II, or III of clinical trials for relapsed patients. This review covers the new strategies, based on clinical trials and our own data and intended for optimizing treatment outcomes in relapsed/refractory multiple myeloma. We describe the various classes of novel drugs under investigation and discuss the pros and cons of the data obtained in preclinical and clinical studies. The adverse effects of the new drugs are presented in detail.

Keywords: multiple myeloma, relapsed/refractory multiple myeloma, bortezomib, thalidomide, lenalidomide, carfilzomib, pomalidomide, treatment, complete remission, overall survival, neuropathy.

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Multiple myeloma (management of newly diagnosed patients): literature review and our on data. Part II

CLINICAL PRESENTATION, DIAGNOSIS, AND MANAGEMENT OF LYMPHOID MALIGNANCIES , , , , , , ,

S.S. Bessmeltsev

Russian Research Institute of Hematology and Transfusiology, FMBA, Saint Petersburg, Russian Federation

ABSTRACT

Over the last decades, survival rates for young patients with multiple myeloma markedly increased mainly due to the use of autologous stem cell transplantation (ASCT) and new highly efficacious rescue therapies. In patients with multiple myeloma over 65 years of age, a combination of melphalan and prednisone (MP) is traditionally used. Introduction of novel agents such as immunomodulatory drugs (IMiDs) and proteasome inhibitors substantially changed the therapeutic approach to the disease. Many double-, triple-, and quadruple-agent combinations were studied in the patients with newly diagnosed multiple myeloma. It was established that the achievement of complete response (CR) is an independent predictor of prolonged progression-free survival (PFS) and overall survival (OS). The data from prospective trials completed suggest that the best available strategy to achieve high CR rates and prolong its duration includes an induction therapy with a triple-agent bortezomib- or IMiDs-based regimen followed by ASCT and consolidation/maintenance with IMiDs or proteasome inhibitors. The vast majority of elderly patients with MM are ineligible for ASCT. Introduction of novel agents such as thalidomide, bortezomib, or lenalidomide considerably improved the treatment outcomes. MPT (MP + thalidomide), VMP (MP + bortezomib), and MPR-R (MP + lenalidomide) regimens are currently regarded as the new standards of care for elderly patients with multiple myeloma. The prognosis for multiple myeloma is determined by numerous factors, all of which should be considered when choosing the initial therapy. This review covers the new strategies based on the current studies being conducted that are aimed at optimizing treatment outcomes in the patients with newly diagnosed multiple myeloma.

Keywords: multiple myeloma, bortezomib, thalidomide, lenalidomide, treatment, complete remission, overall survival, neuropathy, autologous stem cell transplantation

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