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Re-defining Prognosis of Hematological Malignancies by Dynamic Response Assessment Methods: Lessons Learnt in Chronic Myeloid Leukemia, Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma and Multiple Myeloma

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Abstract

Risk-stratification is an essential management tool in defining prognosis of haematological neoplasms, both from patient and physician perspective. We define a new prognostic term “Dynamic Response Assessment Method(s) (DRAM)” as “method(s) used for re-stratifying disease prognosis at fixed intervals during the treatment course”. The risk stratification is done after a fixed duration of treatment or chemotherapy cycles using sensitive techniques. The information obtained then can be used for further therapeutic decisions and prognostication. Currently, there is enough evidence that response to treatment improves the prognostic value of baseline disease variables in the management of Chronic Myeloid Leukemia, Hodgkin lymphoma, Diffuse Large B cell Lymphoma, and Multiple Myeloma. Through this review, we discuss the current evidence based application of “DRAM” to guide therapeutic decisions in these malignancies. We also discuss how the results of “DRAM” can be incorporated for redefining prognosis and counselling the patients with these selected hematologic malignancies.

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References

  1. El-Jawahri A, Traeger L, Kuzmuk K, Eusebio J, Vandusen H, Keenan T et al (2015) Prognostic understanding, quality of life and mood in patients undergoing hematopoietic stem cell transplantation. Bone Marrow Transplant 50(8):1119–1124

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Sokal J, Cox E, Baccarani M, Tura S, Gomez G, Robertson J et al (1984) Prognostic discrimination in chronic granulocytic leukemia. Blood 63(4):789–799

    CAS  PubMed  Google Scholar 

  3. Hasford J, Pfirrmann M, Hehlmann R, Allan NC, Baccarani M, Kluin-Nelemans JC et al (1998) A new prognostic score for survival of patients with chronic Myeloid Leukemia treated with interferon alfa writing committee for the collaborative CML prognostic factors project group. JNCI J Natl Cancer Inst 90(11):850–859

    CAS  PubMed  Google Scholar 

  4. Hasford J, Baccarani M, Hoffmann V, Guilhot J, Saussele S, Rosti G et al (2011) Predicting complete cytogenetic response and subsequent progression-free survival in 2060 patients with CML on imatinib treatment: the EUTOS score. Blood 118(3):686–692

    CAS  PubMed  Google Scholar 

  5. Jabbour E, Cortes J, Nazha A, O’Brien S, Quintas-Cardama A, Pierce S et al (2012) EUTOS score is not predictive for survival and outcome in patients with early chronic phase chronic myeloid leukemia treated with tyrosine kinase inhibitors: a single institution experience. Blood 119(19):4524–4526

    CAS  PubMed Central  PubMed  Google Scholar 

  6. Marin D, Ibrahim AR, Goldman JM (2011) European treatment and outcome study (EUTOS) Score for chronic Myeloid Leukemia still requires more confirmation. J Clin Oncol 29(29):3944–3945

    PubMed  Google Scholar 

  7. Hu B, Savani BN (2014) Impact of risk score calculations in choosing front-line tyrosine kinase inhibitors for patients with newly diagnosed chronic myeloid leukemia in the chronic phase. Eur J Haematol 93(3):179–186

    CAS  PubMed  Google Scholar 

  8. Mahon F-X (2017) Treatment-free remission in CML: who, how, and why? Hematology 2017(1):102–109

    PubMed  PubMed Central  Google Scholar 

  9. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al (2016) The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood 127(20):2391–2405

    CAS  PubMed  Google Scholar 

  10. Bower H, Björkholm M, Dickman PW, Höglund M, Lambert PC, Andersson TM-L (2016) Life expectancy of patients with chronic Myeloid Leukemia approaches the life expectancy of the general population. J Clin Oncol 34(24):2851–2857

    CAS  PubMed  Google Scholar 

  11. Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF et al (2013) European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122(6):872–884

    CAS  PubMed Central  PubMed  Google Scholar 

  12. O’Brien S, Radich JP, Abboud CN, Akhtari M, Altman JK, Berman E et al (2013) Chronic Myelogenous Leukemia, version 1.2014. J Natl Compr Canc Netw. 11(11):1327–1340

    PubMed Central  PubMed  Google Scholar 

  13. Hughes TP, Saglio G, Kantarjian HM, Guilhot F, Niederwieser D, Rosti G et al (2014) Early molecular response predicts outcomes in patients with chronic myeloid leukemia in chronic phase treated with frontline nilotinib or imatinib. Blood 123(9):1353–1360

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Harrington P, Kizilors A, de Lavallade H (2017) The role of early molecular response in the management of chronic phase CML. Curr Hematol Malig Rep 12(2):79–84

    PubMed Central  PubMed  Google Scholar 

  15. Branford S, Yeung DT, Parker WT, Roberts ND, Purins L, Braley JA et al (2014) Prognosis for patients with CML and & < 10% BCR-ABL1 after 3 months of imatinib depends on the rate of BCR-ABL1 decline. Blood 124(4):511–518

    CAS  PubMed  Google Scholar 

  16. Malhotra P, Chikkodi SV, Naseem S, Khadwal A, Prakash G, Kumari S et al (2015) CHR Velocity as a predictor of early molecular response in patients with chronic myeloid leukemia. J Clin Oncol 33(15_suppl):e18038

    Google Scholar 

  17. Barnes G (2015) Burden of tyrosine kinase inhibitor failure in patients with chronic Myeloid Leukemia. J Leuk 3(1):170

    Google Scholar 

  18. Hughes TP, Lipton JH, Spector N, Cervantes F, Pasquini R, Clementino NCD et al (2014) Deep molecular responses achieved in patients with CML-CP who are switched to nilotinib after long-term imatinib. Blood 124(5):729–736

    CAS  PubMed  Google Scholar 

  19. Barnes G (2015) Burden of tyrosine kinase inhibitor failure in patients with chronic Myeloid Leukemia. J Leuk 3(1):170

    Google Scholar 

  20. Cortes JE, Saglio G, Kantarjian HM, Baccarani M, Mayer J, Boqué C et al (2016) Final 5-year study results of DASISION: the dasatinib versus imatinib study in treatment-naïve chronic Myeloid Leukemia patients trial. J Clin Oncol 34(20):2333–2340

    CAS  PubMed Central  PubMed  Google Scholar 

  21. Hochhaus A, Saglio G, Hughes TP, Larson RA, Kim D-W, Issaragrisil S et al (2016) Long-term benefits and risks of frontline nilotinib vs. imatinib for chronic myeloid leukemia in chronic phase: 5-year update of the randomized ENESTnd trial. Leukemia 30(5):1044–1054

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Etienne G, Guilhot J, Rea D, Rigal-Huguet F, Nicolini F, Charbonnier A et al (2017) Long-term follow-up of the french stop imatinib (STIM1) study in patients with chronic Myeloid Leukemia. J Clin Oncol 35(3):298–305

    PubMed  Google Scholar 

  23. Ross DM, Branford S, Seymour JF, Schwarer AP, Arthur C, Yeung DT et al (2013) Safety and efficacy of imatinib cessation for CML patients with stable undetectable minimal residual disease: results from the TWISTER study. Blood 122(4):515–522

    CAS  PubMed  Google Scholar 

  24. Campiotti L, Suter MB, Guasti L, Piazza R, Gambacorti-Passerini C, Grandi AM et al (2017) Imatinib discontinuation in chronic myeloid leukaemia patients with undetectable BCR-ABL transcript level: a systematic review and a meta-analysis. Eur J Cancer 77:48–56

    CAS  PubMed  Google Scholar 

  25. Mahon F, Richter J, Guilhot J, Hjorth-Hansen H, Almeida A, Janssen JJWMJ et al (2016) Cessation of tyrosine kinase inhibitors treatment in chronic Myeloid Leukemia patients with deep molecular response: results of the Euro-Ski trial. Blood 128(22):787

    Google Scholar 

  26. Rea D, Nicolini FE, Tulliez M, Guilhot F, Guilhot J, Guerci-Bresler A et al (2017) Discontinuation of dasatinib or nilotinib in chronic myeloid leukemia: interim analysis of the STOP 2G-TKI study. Blood 129(7):846–854

    CAS  PubMed  Google Scholar 

  27. Imagawa J, Tanaka H, Okada M, Nakamae H, Hino M, Murai K et al (2015) Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained deep molecular response for longer than 1 year (DADI trial): a multicentre phase 2 trial. Lancet Haematol 2(12):e528–e535

    PubMed  Google Scholar 

  28. Hochhaus A, Masszi T, Giles FJ, Radich JP, Ross DM, Gómez Casares MT et al (2017) Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study. Leukemia 31(7):1525–1531

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Hughes TP, Boquimpani C, Kim D-W, Benyamini N, Clementino NCD, Shuvaev V et al (2016) Treatment-free remission (TFR) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) treated with second-line nilotinib (NIL): first results from the ENESTop study. J Clin Oncol 34(15_suppl):7054

    Google Scholar 

  30. Legros L, Nicolini FE, Etienne G, Rousselot P, Rea D, Giraudier S et al (2017) Second tyrosine kinase inhibitor discontinuation attempt in patients with chronic myeloid leukemia. Cancer 123(22):4403–4410

    CAS  PubMed  Google Scholar 

  31. Johnson PWM (2016) Response-adapted frontline therapy for Hodgkin lymphoma: are we there yet? Hematology 2016(1):316–322

    PubMed  PubMed Central  Google Scholar 

  32. Mamot C, Klingbiel D, Hitz F, Renner C, Pabst T, Driessen C et al (2015) Final results of a prospective evaluation of the predictive value of interim positron emission tomography in patients with diffuse large B-cell lymphoma treated with R-CHOP-14 (SAKK 38/07). J Clin Oncol 33(23):2523–2529

    CAS  PubMed  Google Scholar 

  33. Gallamini A, Hutchings M, Rigacci L, Specht L, Merli F, Hansen M et al (2007) Early Interim 2-[18 F]Fluoro-2-Deoxy-d-Glucose positron emission tomography is prognostically superior to international prognostic score in advanced-stage hodgkin’s lymphoma: a report from a joint italian-danish study. J Clin Oncol 25(24):3746–3752

    CAS  PubMed  Google Scholar 

  34. Hoppe RT, Advani RH, Ai WZ, Ambinder RF, Aoun P, Armand P et al (2018) NCCN guidelines insights: hodgkin lymphoma, Version 1.2018. J Natl Compr Cancer Netw 16(3):245–254

    Google Scholar 

  35. Radford J, Illidge T, Counsell N, Hancock B, Pettengell R, Johnson P et al (2015) Results of a trial of PET-directed therapy for early-stage hodgkin’s lymphoma. N Engl J Med 372(17):1598–1607

    CAS  PubMed  Google Scholar 

  36. Raemaekers JMM, André MPE, Federico M, Girinsky T, Oumedaly R, Brusamolino E et al (2014) Omitting radiotherapy in early positron emission tomography-negative stage I/II hodgkin lymphoma is associated with an increased risk of early relapse: clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol 32(12):1188–1194

    PubMed  Google Scholar 

  37. André MPE, Girinsky T, Federico M, Reman O, Fortpied C, Gotti M et al (2017) Early positron emission tomography response-adapted treatment in stage i and ii hodgkin lymphoma: final results of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol 35(16):1786–1794

    PubMed  Google Scholar 

  38. Johnson P, Federico M, Kirkwood A, Fosså A, Berkahn L, Carella A et al (2016) Adapted treatment guided by interim PET-CT scan in advanced hodgkin’s lymphoma. N Engl J Med 374(25):2419–2429

    PubMed Central  PubMed  Google Scholar 

  39. Casasnovas O, Brice P, Bouabdallah R, Salles GA, Stamatoullas A, Dupuis J et al (2015) Randomized phase III study comparing an early pet driven treatment de-escalation to a not pet-monitored strategy in patients with advanced stages hodgkin lymphoma: interim analysis of the AHL2011 Lysa study. Blood 126(23):577

    Google Scholar 

  40. Dann EJ, Bairey O, Bar-Shalom R, Sabbag E, Izak M, Korenberg A et al (2014) Tailored therapy in hodgkin lymphoma, based on predefined risk factors and early interim PET/CT: Israeli H2 study. Blood 124(21):4409

    Google Scholar 

  41. Moskowitz C (2016) Novel agents and strategies in transplant-eligible patients with relapsed and refractory Hodgkin lymphoma. Hematology 2016(1):331–338

    PubMed  PubMed Central  Google Scholar 

  42. Smeltzer JP, Cashen AF, Zhang Q, Homb A, Dehdashti F, Abboud CN et al (2011) Prognostic Significance of FDG-PET in Relapsed or Refractory Classical Hodgkin Lymphoma Treated with Standard Salvage Chemotherapy and Autologous Stem Cell Transplantation. Biol Blood Marrow Transplant 17(11):1646–1652

    PubMed Central  PubMed  Google Scholar 

  43. Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH et al (2015) Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 385(9980):1853–1862

    CAS  PubMed  Google Scholar 

  44. Coiffier B, Thieblemont C, Van Den Neste E, Lepeu G, Plantier I, Castaigne S et al (2010) Long-term outcome of patients in the LNH-985 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d’Etudes des Lymphomes de l’Adulte. Blood 116(12):2040–2045

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Coiffier B, Sarkozy C (2016) Diffuse large B-cell lymphoma: r-CHOP failure–what to do? Hematology 2016(1):366–378

    PubMed  PubMed Central  Google Scholar 

  46. Jiang M, Chen P, Ruan X, Ye X, Pan Y, Zhang J et al (2017) Interim 18F-FDG PET/CT improves the prognostic value of S-IPI, R-IPI and NCCN-IPI in patients with diffuse large B-cell lymphoma. Oncol Lett 14(6):6715–6723

    PubMed Central  PubMed  Google Scholar 

  47. Weiler-Sagie M, Bushelev O, Epelbaum R, Dann EJ, Haim N, Avivi I et al (2010) 18F-FDG avidity in lymphoma readdressed: a study of 766 patients. J Nucl Med 51(1):25–30

    PubMed  Google Scholar 

  48. Huang H, Lin J, Guo C, Li S, Hong H, Li X et al (2015) Predictive value of interim 18 f-FDG PET-CT scans on diffuse large B-cell lymphoma treated with R-CHOP: a prospective study. Blood 126(23):1458

    Google Scholar 

  49. Hertzberg MS, Gandhi MK, Butcher B, Columbus R, Taper J, Trotman J et al (2015) Early treatment intensification with R-ICE chemotherapy followed by autologous stem cell transplantation (ASCT) using zevalin-beam for patients with poor risk diffuse large B-cell lymphoma (DLBCL) as identified by interim PET/CT scan performed after four. Blood 126(23):815

    Google Scholar 

  50. Carr R, Fanti S, Paez D, Cerci J, Gyorke T, Redondo F et al (2014) Prospective international cohort study demonstrates inability of interim pet to predict treatment failure in diffuse large B-Cell lymphoma. J Nucl Med 55(12):1936–1944

    PubMed  Google Scholar 

  51. Huntington SF, Nasta SD, Schuster SJ, Doshi JA, Svoboda J (2015) Utility of interim and end-of-treatment fluorodeoxyglucose positron emission tomography–computed tomography in frontline therapy of patients with diffuse large B-cell lymphoma. Leuk Lymphoma 56(9):2579–2584

    PubMed  Google Scholar 

  52. Burggraaff CN, de Jong A, Hoekstra OS, Hoetjes NJ, Nievelstein RAJ, Jansma EP et al (2019) Predictive value of interim positron emission tomography in diffuse large B-cell lymphoma: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging 46(1):65–79

    PubMed  Google Scholar 

  53. Mamot C, Klingbiel D, Hitz F, Renner C, Pabst T, Driessen C et al (2015) Final results of a prospective evaluation of the predictive value of interim positron emission tomography in patients with diffuse large B-cell lymphoma treated With R-CHOP-14 (SAKK 38/07). J Clin Oncol 33(23):2523–2529

    CAS  PubMed  Google Scholar 

  54. Safar V, Dupuis J, Itti E, Jardin F, Fruchart C, Bardet S et al (2012) Interim [18]Fluorodeoxyglucose positron emission tomography scan in diffuse large B-cell lymphoma treated with anthracycline-based chemotherapy plus rituximab. J Clin Oncol 30(2):184–190

    CAS  PubMed  Google Scholar 

  55. Winter A, Rybicki L, Shah SN, Jagadeesh D, Gerds AT, Hamilton BK et al (2018) Prognostic value of pre-transplant PET/CT in patients with diffuse large B-cell lymphoma undergoing autologous stem cell transplantation. Leuk Lymphoma 59(5):1195–1201

    PubMed  Google Scholar 

  56. Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosinol L et al (2015) Revised international staging system for multiple myeloma: a report from international myeloma working group. J Clin Oncol 33(26):2863–2869

    CAS  PubMed Central  PubMed  Google Scholar 

  57. Majithia N, Vincent Rajkumar S, Lacy MQ, Buadi FK, Dispenzieri A, Gertz MA et al (2015) Outcomes of primary refractory multiple myeloma and the impact of novel therapies. Am J Hematol 90(11):981–985

    CAS  PubMed Central  PubMed  Google Scholar 

  58. Yanamandra U, Kumar SK (2018) Minimal residual disease analysis in myeloma—when, why and where. Leuk Lymphoma 59(8):1772–1784

    PubMed  Google Scholar 

  59. Landgren O, Devlin S, Boulad M, Mailankody S (2016) Role of MRD status in relation to clinical outcomes in newly diagnosed multiple myeloma patients: a meta-analysis. Bone Marrow Transplant 51(12):1565–1568

    CAS  PubMed Central  PubMed  Google Scholar 

  60. Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P et al (2016) International myeloma working group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol 17(8):e328–e346

    PubMed  Google Scholar 

  61. Rasche L, Alapat D, Kumar M, Gershner G, McDonald J, Wardell CP et al (2019) Combination of flow cytometry and functional imaging for monitoring of residual disease in myeloma. Leukemia 33(7):1713–1722

    CAS  PubMed  Google Scholar 

  62. Mailankody S, Korde N, Lesokhin AM, Lendvai N, Hassoun H, Stetler-Stevenson M et al (2015) Minimal residual disease in multiple myeloma: bringing the bench to the bedside. Nat Rev Clin Oncol 12(5):286–295

    PubMed  PubMed Central  Google Scholar 

  63. Gandolfi S, Prada CP, Richardson P, Paba-Prada C. How I treat the young patient with multiple myeloma. Blood First Ed Pap. 2018

  64. Stadtmauer EA, Pasquini MC, Blackwell B, Hari P, Bashey A, Devine S et al (2019) Autologous transplantation, consolidation, and maintenance therapy in multiple myeloma: results of the BMT CTN 0702 trial. J Clin Oncol 37(7):589–597

    CAS  PubMed Central  PubMed  Google Scholar 

  65. Palumbo A, Gay F, Cavallo F, Di Raimondo F, Larocca A, Hardan I et al (2015) Continuous therapy versus fixed duration of therapy in patients with newly diagnosed multiple myeloma. J Clin Oncol 33(30):3459–3466

    CAS  PubMed  Google Scholar 

  66. Wildes TM, Anderson KC (2018) Approach to the treatment of the older, unfit patient with myeloma from diagnosis to relapse: perspectives of a US hematologist and a geriatric hematologist. Hematology 2018(1):88–96

    PubMed  PubMed Central  Google Scholar 

  67. Radich JP (2009) How I monitor residual disease in chronic myeloid leukemia. Blood 114(16):3376–3381

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Cerci JJ, Trindade E, Pracchia LF, Pitella FA, Linardi CCG, Soares J et al (2010) Cost effectiveness of positron emission tomography in patients with hodgkin’s lymphoma in unconfirmed complete remission or partial remission after first-line therapy. J Clin Oncol 28(8):1415–1421

    PubMed  Google Scholar 

  69. Huntington SF, Nasta SD, Schuster SJ, Doshi JA, Svoboda J (2015) Utility of interim and end-of-treatment fluorodeoxyglucose positron emission tomography–computed tomography in frontline therapy of patients with diffuse large B-cell lymphoma. Leuk Lymphoma 56(9):2579–2584

    PubMed  Google Scholar 

  70. Carlson JJ, Eckert B, Zimmerman M. Cost-effectiveness of next-generation sequencing minimal residual disease testing during maintenance treatment for multiple myeloma. Presented at: 2019 American Society of Clinical Oncology Annual Meeting; May 31-June 4, 2019; Chicago, Illinois. Abstract E19529

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  1. Department of Internal Medicine (Clinical Hematology Division), Postgraduate Institute of Medical Education and Research, Chandigarh, 4th Floor, F Block, Nehru Hospital, Chandigarh, 160012, India

    Arihant Jain & Pankaj Malhotra

  2. Department of Hematology, Vardhaman Mahavir Medical College, Safdarjung Hospital, New Delhi, 110029, India

    Ankur Jain

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AJ and AJ contributed equally to the draft. PM was involved in draft conception and supervision. All the authors reviewed the manuscript before submission.

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Correspondence to Pankaj Malhotra.

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Jain, A., Jain, A. & Malhotra, P. Re-defining Prognosis of Hematological Malignancies by Dynamic Response Assessment Methods: Lessons Learnt in Chronic Myeloid Leukemia, Hodgkin Lymphoma, Diffuse Large B Cell Lymphoma and Multiple Myeloma. Indian J Hematol Blood Transfus 36, 447–457 (2020). https://doi.org/10.1007/s12288-019-01213-7

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