The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity

LYMPHOID TUMORS , , ,

KD Kaplanov1,2,3, TYu Klitochenko1,3, AL Shipaeva1, MN Shirokova1, IV Matveeva1, NB Lavrishina1

1 Volgograd Regional Clinical Oncology Dispensary, 78 Zemlyachki str., Volgograd, Russian Federation, 400138

2 Volgograd Medical Research Center, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

3 Volgograd State Medical University, 1 Pavshikh Bortsov pl., Volgograd, Russian Federation, 400131

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

For citation: Kaplanov KD, Klitochenko TYu, Shipaeva АL, et al. The IVDG Regimen is the Possible Treatment of Choice as First Line Therapy For Hodgkin’s Lymphoma in Elderly Patients with Cardiovascular and Pulmonary Comorbidity. Clinical oncohematology. 2017;10(3):358–65 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-358-365

ABSTRACT

Background. Among the newly diagnosed patients with Hodgkin’s lymphoma (HL), the proportion of elderly patients account for 15–35 %. In > 60 age group the choice of antitumor treatment requires an more individualised approach compared to a younger population. The ABVD regimen is acceptable in terms of efficiency and hematological toxicity, but is associated with a high risk of bleomycine-induced pulmonary complications. In ≥ 60 age group the morbitity and mortality of pulmonary complications account for 24 % and 18 %, respectively.

Aim. We aimed to evaluate the efficacy of the IVDG regimen in comparison with ABVD by the principle of “non-inferiority”.

Materials & Methods. This single centre, prospective, controlled, randomised study was started in 2009. The study included all primary patients aged ≥ 60 years with verified HL, regardless of the number and severity of comorbidities. The ABVD regimen was administered in 17 patients, and 20 patients received IVDG. The median age in the ABVD and IVDG groups was 67 and 70 years, respectively. The advanced stages of HL were reported in 13 (65 %) patients on IVDG, and in 12 (71 %) patients on ABVD (p = 0.9). Both of the groups were comparable in terms of the prevalence of chronic heart failure and chronic obstructive pulmonary disease. The prevalence of ischemic heart disease was higher in the IVDG group (n = 16) compared to ABVD (n = 8) (p = 0.04).

Results. IVDG and ABVD groups did not differ in the frequency of complete (14 and 10) and partial (3 and 4) remissions. Differences in 5-year overall survival were insignificant: 49 % in the IVDG group, vs 22 % in ABVD group (p = 0.41). No infectious or hemorrhagic complications were observed in both groups. The incidence of drug-induced pulmonary fibrosis after treatment was significantly lower in the IVDG group (n = 0) vs ABVD group (n = 4; 24 %) (p = 0.004).

Conclusion. The IVDG regimen may be used as first line treatment for HL in the elderly patients, especially in those having cardiac or pulmonary comorbidities. Compared to ABVD the IVDG regimen had similar efficacy and more beneficial safety profile in terms of cardiovascular and pulmonary toxicity.

Keywords: Hodgkin’s lymphoma, elderly patients, comorbidity, chemotherapy.

Received: December 22, 2016

Accepted: March 5, 2017

Read in PDF (RUS)pdficon

REFERENCES

  1. Landgren O, Algernon C, Axdorph U, et al. Hodgkin’s lymphoma in the elderly with special reference to type and intensity of chemotherapy in relation to prognosis. Haematologica. 2003;88(4):438–44.
  2. Engert A, Ballova V, Haverkamp H, et al. Hodgkin’s lymphoma in elderly patients: a comprehensive retrospective analysis from the German Hodgkin’s Study Group. J Clin Oncol. 2005;23(22):5052–60. doi: 10.1200/jco.2005.11.080.
  3. Evens AM, Helenowski I, Ramsdale E, et al. A retrospective multicenter analysis of elderly Hodgkin lymphoma: outcomes and prognostic factors in the modern era. Blood. 2012;119(3):692–5. doi: 10.1182/blood-2011-09-378414.
  4. Stark GL, Wood KM, Jack F, et al. Hodgkin’s disease in the elderly: a population-based study. Br J Haematol. 2002;119(2):432–40. doi: 10.1046/j.1365-2141.2002.03815.x.
  5. Hasenclever D, Diehl V. A prognostic score for advanced Hodgkin’s disease. International Prognostic Factors Project on advanced Hodgkin’s Disease. N Engl J Med. 1998;339(21):1506–14.
  6. Evens AM, Hong F, Gordon LI, et al. The efficacy and tolerability of adriamycin, bleomycin, vinblastine, dacarbazine and Stanford V in older Hodgkin lymphoma patients: a comprehensive analysis from the North American intergroup trial E2496. Br J Haematol. 2013;161(1):76–86. doi: 10.1111/bjh.12222.
  7. Ballova V, Ruffer JU, Haverkamp H, et al. A prospectively randomized trial carried out by the German Hodgkin Study Group (GHSG) for elderly patients with advanced Hodgkin’s disease comparing BEACOPP baseline and COPP-ABVD (study HD9elderly). Ann Oncol. 2005;16(1):124–31. doi: 10.1093/annonc/mdi023.
  8. Halbsguth TV, Nogova L, Mueller H, et al. Phase 2 study of BACOPP (bleomycin, adriamycin, cyclophosphamide,vincristine, procarbazine, and prednisone) in older patients with Hodgkin lymphoma: a report from the German Hodgkin Study Group (GHSG). Blood. 2010;116(12):2026–32. doi: 10.1182/blood-2009-11-253211.
  9. Levis A, Anselmo AP, Ambrosetti A, et al. VEPEMB in elderly Hodgkin’s lymphoma patients. Results from an Intergruppo Italiano Linfomi (IIL) study. Ann Oncol. 2004;15(1):123–8. doi: 10.1093/annonc/mdh012.
  10. Proctor SJ, Wilkinson J, Jones G, et al. Evaluation of treatment outcome in 175 patients with Hodgkin lymphoma aged 60 years or over: the SHIELD study. Blood. 2012;119(25):6005–15. doi: 10.1182/blood-2011-12-396556.
  11. Boll B, Bredenfeld H, Gorgen H, et al. Phase 2 study of PVAG (prednisone, vinblastine, doxorubicin, gemcitabine) in elderly patients with early unfavorable or advanced stage Hodgkin lymphoma. Blood. 2011;118(24):6292–8. doi: 10.1182/blood-2011-07-368167.
  12. Boll B, Gorgen H, Fuchs M, et al. ABVD in older early stage Hodgkin lymphoma patients treated within the German Hodgkin Study Group (GHSG) HD10 and HD11 Trials. J Clin Oncol. 2013;31(12):1522–9. doi: 10.1200/jco.2012.45.4181.
  13. Weekes CD, Vose JM, Lynch JC, et al. Hodgkin’s disease in the elderly: improved treatment outcome with a doxorubicin-containing regimen. J Clin Oncol. 2002;20(4):1087–93. doi: 10.1200/jco.20.4.1087.
  14. Behringer K, Goergen H, Hitz F, et al. Omission of dacarbazine or bleomycin, or both, from the ABVD regimen in treatment of early-stage favourable Hodgkin’s lymphoma (GHSG HD13): an open-label, randomised, non-inferiority trial. Lancet. 2015;385(9976):1418. doi: 10.1016/s0140-6736(14)61469-0.
  15. Леонтьева А.А., Демина Е.А. Лечение распространенных стадий лимфомы Ходжкина: обзор литературы. Клиническая онкогематология. 2015;8(3):255–66. doi: 10.21320/2500-2139-2015-8-3-255-266.
    [Leont’eva AA, Demina EA. Treatment of Advanced Stage Hodgkin’s Lymphoma: Literature Review. Clinical oncohematology. 2015;8(3):255–66. doi: 10.21320/2500-2139-2015-8-3-255-266. (In Russ)]
  16. Borchmann P, Eichenauer DA, Pluetschow A, et al. Targeted BEACOPP variants in patients with newly diagnosed advanced stage classical Hodgkin lymphoma: Final analysis of a randomized phase II study. Blood. 2015;126:580 (abstract).
  17. Российские клинические рекомендации по диагностике и лечению лимфопролиферативных заболеваний. Под ред. И.В. Поддубной, В.Г. Савченко. М.: Буки Веди, 2016. С. 29–30.
    [Poddubnaya IV, Savchenko VG, eds. Rossiiskie klinicheskie rekomendatsii po diagnostike i lecheniyu limfoproliferativnykh zabolevanii. (Russian clinical guidelines in diagnosis and treatment of lymphoproliferative disorders). Moscow: Buki Vedi Publ.; 2016. pp. 29–30. (In Russ)]
  18. Forero-Torres A, Holkova B, Goldschmidt J, et al. Phase 2 study of frontline brentuximab vedotin monotherapy in Hodgkin lymphoma patients aged 60 years and older. Blood. 2015;126(26):2798–804. doi: 10.1182/blood-2015-06-644336.
  19. Enblad G, Gustavsson A, Sundstrom C, Glimelius B. Patients above sixty years of age with Hodgkin’s lymphoma treated with a new strategy. Acta Oncol. 2002;41(7):659–67. doi: 10.1080/028418602321028283.
  20. Kim HK, Silver B, Li S, et al. Hodgkin’s disease in elderly patients (≥60): Clinical outcome and treatment strategies. Int J Radiat Oncol Biol Phys. 2003;56(2):556–60. doi: 10.1016/s0360-3016(02)04596-0.
  21. Van Spronsen DJ, Janssen-Heijnen MLG, Lemmens VEPP, et al. Independent prognostic effect of co-morbidity in lymphoma patients: results of the population-based Eindhoven Cancer Registry. Eur J Cancer. 2005;41(7):1051–7. doi: 10.1016/j.ejca.2005.01.010.
  22. Macpherson N, Klasa RJ, Gascoyne R, et al. Treatment of elderly Hodgkin’s lymphoma patients with a novel 5-drug regimen (ODBEP): a phase II study. Leuk Lymphoma. 2002;43(7):1395–402. doi: 10.1080/10428190290033332.
  23. Kolstad A, Nome O, Delabie J, et al. Standard CHOP-21 as first line therapy for elderly patients with Hodgkin’s lymphoma. Leuk Lymphoma 2007;48(3):570–6. doi: 10.1080/10428190601126610.
  24. Klimm B, Eich HT, Haverkamp H, et al. Poorer outcome of elderly patients treated with extended-field radiotherapy compared with involved-field radiotherapy after chemotherapy for Hodgkin’s lymphoma: an analysis from the German Hodgkin Study Group. Ann Oncol. 2007;18(2):357–63. doi: 10.1093/annonc/mdl379.