Quality of Life and Efficacy of Triplet IxaRd Therapy in Relapsed/Refractory Multiple Myeloma: Results of a Multi-Center Pilot Real-World Study

AUTOIMMUNE THROMBOCYTOPENIA ,

TI Ionova1,2, OYu Vinogradova3,4,5, YuB Kochkareva3, EE Markova3, KD Kaplanov6, MN Shirokova6,7, TV Shelekhova8, AN Levanov8, AV Kopylova9, OYu Li10, TA Mitina11, OA Rukavitsyn12, PI Simashova12, LV Anchukova13, EN Babich14, SA Volkova15, DB Dasheeva16, MV Demchenkova17, SK Dubov18, TV Esenina19, LE Ivanova17, TL Kravchuk20, EV Rimashevskaya21, MT Savinova22, NO Saraeva23, NM Porfirieva1, TP Nikitina1,2, VV Ptushkin3

1 Multinational Center for Quality of Life Research, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014

2 Saint Petersburg State University Hospital, 154 Fontanki nab., Saint Petersburg, Russian Federation, 198103

3 Moscow Municipal Center for Hematology, SP Botkin City Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

4 NI Pirogov Russian National Research Medical University, 1 Ostrovityanova ul., Moscow, Russian Federation, 117997

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

6 SP Botkin City Clinical Hospital, 5 2-i Botkinskii pr-d, Moscow, Russian Federation, 125284

7 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki ul., Volgograd, Russian Federation, 400138

8 VI Razumovskii Saratov State Medical University, 112 Bolshaya Kazach’ya ul., Saratov, Russian Federation, 410012

9 Lipetsk Municipal Hospital No. 3 “Svobodnyi sokol”, 10 Ushinskogo ul., Lipetsk, Russian Federation, 398007

10 Sakhalin Regional Clinical Hospital, 430 Mira pr-t, Yuzhno-Sakhalinsk, Russian Federation, 693004

11 MF Vladimirskii Moscow Regional Research Clinical Institute, 61/2 Shchepkina ul., Moscow, Russian Federation, 129110

12 NN Burdenko Main Military Clinical Hospital, 3 Gospital’naya pl., Moscow, Russian Federation, 105094

13 Vologda Regional Clinical Hospital, 17 Lechebnaya ul., Vologda, Russian Federation, 160002

14 Yugry District Clinical Hospital, 40 Kalinina ul., Khanty-Mansiisk, Russian Federation, 628011

15 Privolzhsky Research Medical University, 10/1 Minina i Pozharskogo pl., Nizhny Novgorod, Russian Federation, 603005

16 Zabaikalsky Krai Oncology Dispensary, 104 Leningradskaya ul., Chita, Russian Federation, 672027

17 Irkutsk Regional Cancer Center, 32 Frunze ul., Irkutsk, Russian Federation, 664035

18 Krai Clinical Hospital No. 2, 55 Russkaya ul., Vladivostok, Russian Federation, 690105

19 Amurskaya Regional Clinical Hospital, 26 Voronkova ul., Blagoveshchensk, Russian Federation, 675000

20 Tomsk National Research Medical Center, 5 Kooperativnyi per., Tomsk, Russian Federation, 634009

21 Russian Medical Academy of Postgraduate Education, 38 Smolnaya ul., Moscow, Russian Federation, 125445

22 Municipal Clinical Hospital No. 16, 121 Gagarina ul., Kazan, Russian Federation, 420039

23 Irkutsk Regional Clinical Hospital, 100 Yubileinyi mikroraion, Irkutsk, Russian Federation, 664049

For correspondence: Tatyana Pavlovna Nikitina, MD, PhD, 1 Artilleriiskaya ul., Saint Petersburg, Russian Federation, 191014; Tel.: +7(962)710-17-12; e-mail: qolife@mail.ru

For citation: Ionova TI, Vinogradova OYu, Kochkareva YuB, et al. Quality of Life and Efficacy of Triplet IxaRd Therapy in Relapsed/Refractory Multiple Myeloma: Results of a Multi-Center Pilot Real-World Study. Clinical oncohematology. 2022;15(3):240–52. (In Russ).

DOI: 10.21320/2500-2139-2022-15-3-240-252

ABSTRACT

Aim. To study quality of life (QoL) indicators and symptom profile as well as treatment satisfaction of patients with relapsed/refractory multiple myeloma (r/r MM) on triplet therapy based on ixazomib combined with lenalidomide and dexamethasone (IxaRd); to assess efficacy and safety of IxaRd protocol in real-world clinical practice.

Materials & Methods. The study enrolled 40 patients with confirmed r/r MM diagnosis, aged > 18 years, at 18 Russian health care institutions. They received at least one line of prior therapy and were IxaRd-eligible. Clinical and QoL indicators were assessed according to the RAND SF-36, and symptoms were evaluated using the ESAS-R questionnaire prior to IxaRd therapy and in 1, 3, 6, 9, 12, 15, and 18 months after its start. Besides, patients filled out checklists for assessment of treatment satisfaction at all time-points after therapy onset. The analysis of clinical IxaRd efficacy included assessment of treatment response by IMWG 2011 criteria, as well as response duration, overall survival (OS), and progression-free survival (PFS). The analysis of IxaRd safety was based on reporting adverse events (AEs), including severe ones (SAEs). To analyze patient-reported QoL and symptom changes during follow-up, GEE was used. To determine clinically meaningful changes, an effect size was calculated.

Results. The study included 40 r/r MM patients (mean age 63 ± 9 years, 65 % women). Median disease duration before IxaRd therapy onset was 55 months (range 2–99 months). 60 % of patients had IIIA/IIIB Durie-Salmon stage. With the median IxaRd duration of 7.5 months, clinical benefit rate was 71.8 %. Complete response was reported in 7.7 % of patients, stringent complete response in 2.6 % of patients, very good partial response in 5.1 % of patients, partial response in 30.8 % of patients, and minor response was achieved in 25.6 % of patients. Stable disease was reported in 15.4 % of patients, and disease progression was identified in 10.3 % patients, including immunochemical relapse in 1 patient. The median response duration was 16.3 months (95% confidence interval [95% CI] 15.4–17.3 months), the median PFS was 10.6 months (95% CI 6.3–16.3 months). The median OS was not reached; the 1-year OS after IxaRd therapy onset was 85.2 % (95% CI 71–99 %). AEs on IxaRd therapy were reported in 55 % of patients, SAEs were reported in 3 (7.5 %) patients. Positive QoL changes were observed on IxaRd therapy. QoL improvement was meaningful in terms of physical functioning, role-physical functioning, general health, vitality, and mental health, compared to baseline. Moreover, a considerable decrease of pain, fatigue, and nausea was revealed. On the whole, 87.5 % of patients were satisfied with the triplet IxaRd therapy.

Conclusion. The results of the present pilot study demonstrate efficacy and safety of the triplet IxaRd therapy (all per os) in real-world clinical practice from r/r MM patients’ and physicians’ perspective. Our data testify to the importance of patients’ feedback in the evaluation of therapy efficacy.

Keywords: multiple myeloma, relapsed/refractory, ixazomib, quality of life, real-world clinical practice.

Received: March 16, 2022

Accepted: June 6, 2022

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REFERENCES

  1. Менделеева Л.П., Вотякова О.М., Рехтина И.Г. и др. Множественная миелома. Современная онкология. 2020;22(4):6–28. doi: 10.26442/18151434.2020.4.200457.
    [Mendeleeva LP, Votiakova OM, Rekhtina IG., et al. Multiple myeloma. Journal of Modern Oncology. 2020;22(4):6–28. doi: 26442/18151434.2020.4.200457. (In Russ)]
  2. Dimopoulos MA, Moreau P, Terpos E, et al. Multiple myeloma: EHA-ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2021;32(3):309–22. doi: 10.1016/j.annonc.2020.11.014.
  3. Costa LJ, Omel J, Brown EE. Recent Trends in Multiple Myeloma Incidence and Survival By Age, Race and Ethnicity in the US. Blood. 2016;128(22):4774. doi: 10.1182/blood.V128.22.4774.4774.
  4. Bazarbachi AH, Al Hamed R, Malard F, et al. Relapsed refractory multiple myeloma: a comprehensive overview. Leukemia. 2019;33:2343–57. doi: 10.1038/s41375-019-0561-2.
  5. Novik A, Salek S, Ionova T (eds). Guidelines. Patient-reported outcomes in hematology. Genoa: Forum service editore; 2012. 203 p.
  6. Sonneveld P, Verelst SG, Lewis P, et al. Review of health-related quality of life data in multiple myeloma patients treated with novel agents. Leukemia. 2013;27(10):1959–69. doi: 10.1038/leu.2013.185.
  7. Kvam AK, Waage A. Health-related quality of life in patients with multiple myeloma – does it matter? Haematologica. 2015;100(6):704–5. doi: 10.3324/haematol.2015.127860.
  8. Nielsen LK, Jarden M, Andersen CL, et al. A systematic review of health-related quality of life in longitudinal studies of myeloma patients. Eur J Haematol. 2017;99(1):3–17. doi: 10.1111/ejh.12882.
  9. Galinsky J, Richard S. Patient Reported Outcome Measures (PROMs) in myeloma: are they fit for the future? 2018. Myeloma UK; 2018.
  10. Sonneveld P, De Witb E, Moreau P. How have evolutions in strategies for the treatment of relapsed/refractory multiple myeloma translated into improved outcomes for patients? Cri Rev Oncol Hematol. 2017;112:153–70. doi: 10.1016/j.critrevonc.2017.02.007.
  11. Cook G, Zweegman S, Mateos MV, et al. A question of class: treatment options for patients with relapsed and/or refractory multiple myeloma. Crit Rev Oncol Hematol. 2018;121:74–89. doi: 10.1016/j.critrevonc.2017.11.016.
  12. Tabayashi T. Management of multiple myeloma in the relapsed/refractory patient. Rinsho Ketsueki. 2019;60(9):1257–64. doi: 10.11406/rinketsu.60.1257.
  13. Рехтина И.Г., Менделеева Л.П. Эффективность помалидомидсодержащих программ у больных множественной миеломой при рефрактерности к леналидомиду. Онкогематология. 2019;14(1):8–13. doi: 10.17650/1818-8346-2019-14-1-8-13.
    [Rekhtina IG, Mendeleeva LP. Efficiency of pomalidomide therapy in patients with multiple myeloma refractory to lenalidomide. Oncohematology 2019;14(1):8–13. doi: 10.17650/1818-8346-2019-14-1-8-13. (In Russ)]
  14. Жеребцова В.А., Воробьев В.И., Гемджян Э.Г. и др. Карфилзомиб, леналидомид и дексаметазон в терапии рецидивов и рефрактерного течения множественной миеломы в реальной клинической практике. Терапевтический архив. 2021;93(7):785–92. doi: 10.26442/00403660.2021.07.200956.
    [Zherebtsova VA, Vorobyev VI, Gemdzhian EG, et al. Carfilzomib, lenalidomide and dexamethasone in relapsed/refractory multiple myeloma patients: the real-life experience. Terapevticheskii arkhiv. 2021;93(7):785–92. doi: 10.26442/00403660.2021.07.200956. (In Russ)]
  15. Moreau P, Masszi T, Grzasko N, et al. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016;374(17):1621–34. doi: 10.1056/NEJMoa1516282.
  16. Brayer J, Baz R. The potential of ixazomib, a second generation proteasome inhibitor, in the treatment of multiple myeloma. Ther Adv Hematol. 2017;8(7):209–20. doi: 10.1177/2040620717710171.
  17. Richardson PG, Kumar S, Laubach JP, et al. New developments in the management of relapsed/refractory multiple myeloma – the role of ixazomib. J Blood Med. 2017;8:107–21. doi: 10.2147/jbm.s102328.
  18. Семочкин С.B. Иксазомиб в лечении рецидивирующей множественной миеломы. Медицинский совет. 2018;10:84–91. doi: 10.21518/2079-701X-2018-10-84-91.
    [Semochkin SV. Ixazomib in the treatment of relapsed multiple myeloma. Meditsinskiy sovet. 2018;10:84–91. doi: 10.21518/2079-701X-2018-10-84-91. (In Russ)]
  19. Ludwig H, Ponisch W, Knop S, et al. Quality of life in patients with relapsed/refractory multiple myeloma during ixazomib-thalidomide-dexamethasone induction and ixazomib maintenance therapy and comparison to the general population. Leuk Lymphoma. 2020;61(2):377–86. doi: 10.1080/10428194.2019.1666381.
  20. Пядушкина Е.А., Деркач Е.В., Игнатьева В.И. и др. Организационно-экономические аспекты применения триплетов в терапии рецидивирующей и рефрактерной множественной миеломы в условиях российского здравоохранения. ФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология. 2021;14(2):136–50. doi: 10.17749/2070-4909/farmakoekonomika.2021.098.
    [Pyadushkina ЕА, Derkach ЕV, Ignatyeva VI, et al. Organizational and economic aspects of triplet therapy of relapsed/refractory multiple myeloma in the Russian healthcare setting. FARMAKOEKONOMIKA. Modern Pharmacoeconomics and Pharmacoepidemiology. 2021;14(2):136–50. doi: 10.17749/2070-4909/farmakoekonomika.2021.098. (In Russ)]
  21. Davies F, Rifkin R, Costello C, et al. Real-world comparative effectiveness of triplets containing bortezomib (B), carfilzomib (C), daratumumab (D), or ixazomib (I) in relapsed/refractory multiple myeloma (RRMM) in the US Ann Hematol. 2021;100:2325–37. doi: 10.1007/s00277-021-04534-8.
  22. Terpos E, Ramasamy K, Maouche N, et al. Real-world effectiveness and safety of ixazomib-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma. Ann Hematol. 2020;99(5):1049–61. doi: 10.1007/s00277-020-03981-z.
  23. Yang Y, Xia ZJ, Zhang WH, et al. The efficacy and safety profile of ixazomib/lenalidomide/dexamethasone in relapsed/refractory multiple myeloma: a multicenter real-world study in China. Zhonghua Xue Ye Xue Za Zhi. 2021;42(8):628–34. doi: 10.3760/cma.j.issn.0253-2727.2021.08.003.
  24. Hajek R, Minarik J, Straub J, et al. Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma. Future Oncol. 2021;17(19):2499–512. doi: 10.2217/fon-2020-1225.
  25. Varga G, Nagy Z, Demeter J, et al. Real World Efficacy and Safety Results of Ixazomib Lenalidomide and Dexamethasone Combination in Relapsed/Refractory Multiple Myeloma: Data Collected from the Hungarian Ixazomib Named Patient Program. Pathol Oncol Res. 2019;25(4):1615–20. doi: 10.1007/s12253-019-00607-2.
  26. Менделеева Л.П., Вотякова О.М., Покровская О.С. и др. Национальные клинические рекомендации по диагностике и лечению множественной миеломы. Гематология и трансфузиология. 2016;61(1, прил. 2):1–24. doi: 10.18821/0234-5730-2016-61-1-S2-1-24.
    [Mendeleeva LP, Votyakova OM, Pokrovskaya OS, et al. National clinical guidelines on diagnosis and treatment of multiple myeloma. Gematologiya i transfuziologiya. 2016;61(1, Suppl 2):1–24. doi: 10.18821/0234-5730-2016-61-1-S2-1-24. (In Russ)]
  27. Durie BGM, Salmon SE. A clinical staging system for multiple myeloma. Correlation of measure myeloma cell mass with presenting clinical features, response to treatment, and survival. Cancer. 1975;36(3):842–54. doi: 10.1002/1097-0142(197509)36:3<842::aid-cncr2820360303>3.0.co;2-u.
  28. Greipp PR, San Miguel JF, Durie BG, et al. International Staging System for Multiple Myeloma. J Clin Oncol. 2005;23(15):3412–20. doi: 10.1200/JCO.2005.04.242.
  29. Rajkumar SV, Harousseau J-L, Durie B, et al. Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1. 2011;117(18):4691–5. doi: 10.1182/blood-2010-10-299487.
  30. Common Terminology Criteria for Adverse Evens (CTCAE 4) Version 4.0. Available from: https://evs.nci.nih.gov/ftp1/CTCAE/CTCAE4.032010-06-14QuickReference5х7.pdf (accessed 28.03.2022).
  31. Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis. 1987;40(5):373–83. doi: 10.1016/0021-9681(87)90171-8.
  32. Hays RD, Sherbourne CD, Mazel RM. User’s manual for medical outcomes study (MOS) core measures of health-related quality of life. RAND Corporation, 1995; MR-162-RC. Available from: www.rand.org (accessed 28.03.2022).
  33. Novik AA, Ionova TI, Kishtovich AV, et al. Stratification of patients using QoL parameters by the method of integral profiles. Quality Life Res. 2003;12(7):770.
  34. Bruera E, Kuehn N, Miller MJ, et al. The Edmonton Symptom Assessment System (ESAS): a simple method of the assessment of palliative care patients. J Palliat Care. 1991;7:6–9.
  35. Watanabe SM, Nekolaichuk C, Beaumont C, et al. A multi-centre comparison of two numerical versions of the Edmonton Symptom Assessment System in palliative care patients. J Pain Symptom Manage. 2011;41(2):456–68. doi: 10.1016/j.jpainsymman.2010.04.020.
  36. Atkinson MJ, Sinha A, Hass SL, et al. Validation of a general measure of treatment satisfaction, the Treatment Satisfaction Questionnaire for Medication (TSQM), using a national panel study of chronic disease. Health Qual Life Outcomes. 2004;2:12. doi: 10.1186/1477-7525-2-12.
  37. Morris SB, DeShon RP. Combining effect size estimates in meta-analysis with repeated measures and independent-groups designs. Psychol Methods. 2002;7(1):105–25. doi: 10.1037/1082-989x.7.1.105.
  38. Angst F, Aeschlimanna A, Angst J. The minimal clinically important difference raised the significance of outcome effects above the statistical level, with methodological implications for future studies. J Clin Epidemiol. 2017;82:128–36. doi: 10.1016/j.jclinepi.2016.11.016.
  39. Revicki D, Hays RD, Cella DE, Sloan J. Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J Clin Epidemiol. 2008;61(2):102–9. doi: 10.1016/j.jclinepi.2007.03.012.
  40. Виноградова О.Ю., Птушкин В.В., Черников М.В. и др. Эпидемиология множественной миеломы в городе Москва. Терапевтический архив. 2019;91(7):83–92. doi: 10.26442/00403660.2019.07.000305.
    [Vinogradova OYu, Ptushkin VV, Chernikov MV, et al. Epidemiology of multiple myeloma in city Moscow. Terapevticheskii arkhiv. 2019;91(7):83–92. doi: 10.26442/00403660.2019.07.000305. (In Russ)]
  41. Семочкин С.В. Длительная непрерывная терапия как новая стратегия лечения рецидивирующей или рефрактерной множественной миеломы. Онкогематология. 2020;15(2):29–41. doi: 10.17650/1818-8346-2020-15-2-29-41.
    [Semochkin SV. Long-term continuous treatment as a new strategy for relapsed or refractory multiple myeloma. Oncohematology. 2020;15(2):29–41. doi: 10.17650/1818-8346-2020-15-2-29-41. (In Russ)]
  42. Семочкин С.В. Новые ингибиторы протеасомы в терапии множественной миеломы. Онкогематология. 2019;14(2):29–40. doi: 10.17650/1818-8346-2019-14-2-29-40.
    [Semochkin SV. New proteasome inhibitors in the management of multiple myeloma. Oncohematology. 2019;14(2):29–40. doi: 10.17650/1818-8346-2019-14-2-29-40. (In Russ)]
  43. Pozzi S, Bari A, Pecherstorfer M, Vallet S. Management of Adverse Events and Supportive Therapy in Relapsed/Refractory Multiple Myeloma. Cancers. 2021;13(19):4978. doi: 10.3390/cancers13194978.