Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Challenges and Changing Trends in the Treatment of Haematological Cancers


Affiliations
1 Haematologist, Lilavati Hospital and Research Centre; Empire Haematology Oncology Centre, Bandra west, Mumbai, India
2 Fellow in Haematology, Lilavati Hospital and Research Centre, Bandra West, Mumbai, India
3 Clinical Assistant, Empire Haematology Oncology Centre, Bandra west, Mumbai, India
     

   Subscribe/Renew Journal


Chemotherapy and radiotherapy were the only weapons against cancer in the past. Research has opened up many vistas for treatment— different classes of drugs, targeted therapy, monoclonal antibodies and immunotherapy to name a few—that have become available in routine practice for the treatment of cancer. This was possible due to research grants/funds and pharma interest to detect new antigens with pharmacogenomics that identified targetable drugs against the antigens on the malignant cells. Disease eradication was the end point in the past that was achieved with great difficulty. With novel agents targeting different antigens through new drug routes and newer drug combinations, including “chemotherapy free” treatment, we seem to be doing better with less toxicity in treatment naïve and relapsed patients, who can now get another shot
at a disease-free survival or clinical remission. Currently many protocols utilise a combination of drugs- one belonging to the older generations and one novel agent (chemoimmunotherapy), a combination of new agents (chemotherapy free protocols), or a combination of subcutaneous and oral medications in the treatment of various malignancies. Futuristically, our aim is to use therapy which avoids / reduces hospitalization with a finite duration of therapy, making treatment cost-effective and more compliant leading to better and deeper malignant cell destruction. However, with the ever evolving and mutating
cancer cell for its survival, novel drugs will become old tomorrow and our protocols, combinations and sequencing of drugs will change over time with the advent of new drugs. The singular end point in cancer treatment today is better efficacy, safety and user-friendly protocols (oral or subcutaneous routes) that will achieve a deep response - undetectable minimal residual disease (uMRD) that will ultimately lead to treatment discontinuation. This in turn will improve compliance, prevent unnecessary toxicity and hopefully provide a functional cure. We are nearly there but we still do not routinely use the word
cure…yet! Hopefully someday.

Keywords

Malignancy, Chemotherapy, novel agents, chemoimmunotherapy, targeted therapy, monoclonal antibodies, uMRD
Subscription Login to verify subscription
User
Notifications
Font Size


  • Moreno A, Colon-Otero G, Solberg LA Jr. The prednisone dosage in the CHOP chemotherapy regimen for non-Hodgkin’s lymphomas (NHL): is there a standard? Oncologist. 2000;5(3):238-49. DOI: 10.1634/theoncologist.5-3-238. PMID: 10884502.
  • DeBoer R, Shyirambere C, Driscoll C, Butera Y, Paciorek A, Ruhangaza D et al. Treatment of Hodgkin lymphoma with ABVD chemotherapy in rural Rwanda: amodel for cancer care delivery implementation. JCO Global Oncology. 2020;(6):1093-1102.
  • Rausch C, Jabbour E, Kantarjian H, Kadia T. Optimizing the use of the hyper CVAD regimen: Clinical vignettes and practical management. Cancer. 2019;126(6):1152-1160.
  • Ikehara S, Shi M, Li M. Novel conditioning regimens for bone marrow transplantation. Blood and Lymphatic Cancer: Targets and Therapy. 2013;1.
  • Fischer K, Cramer P, Stilgenbauer S, Busch R, Balleisen L, Kilp J et al. Bendamustine combined with Rituximab (BR) in first-line therapy of advanced CLL: A multicenter Phase II Trial of the German CLL Study Group (GCLLSG). Blood. 2009;114(22):205-205.
  • Donthireddy V, Shurafa M, Saleh M, Kamboj G, Wang D, Janakiraman N. The Treatment of complicated and high risk chronic Lymphocytic Leukemia (CLL) with Fludarabine, Cyclophosphamide and Rituximab (FCR). Blood. 2005;106(11):5038-5038.
  • Bewarder M, Stilgenbauer S, Thurner L, KadduMulindwa D. Current Treatment Options in CLL. Cancers. 2021;13(10):2468.
  • Ghosh N, Brander D, Mato A, Sharman J, Gutierrez M, Naganuma M et al. CLL-074: Insights From the informCLL Registry: Real-World Application of NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL). Clinical Lymphoma Myeloma and Leukemia. 2021;21:S317.
  • Bhreathnach Ú, Langabeer S. Quantification of atypical BCRABL1 fusion transcripts in patients with chronic myeloid leukemia: Which approach for harmonization?. International Journal of Laboratory Hematology. 2021.
  • Riva G, Nasillo V, Ottomano A, Bergonzini G, Paolini A, Forghieri F et al. Multiparametric Flow Cytometry for MRD Monitoring in Hematologic Malignancies: Clinical Applications and New Challenges. Cancers. 2021;13(18):4582.
  • Rodríguez-Vicente A, Bikos V, Hernández-Sánchez M, Malcikova J, Hernández-Rivas J, Pospisilova S. Nextgeneration sequencing in chronic lymphocytic leukemia: recent findings and new horizons. Oncotarget. 2017;8(41):7123471248.
  • Al-Sawaf O, Fink A, Robrecht S, Sinha A, Tandon M, Eichhorst B et al. Prevention and Management of Tumor Lysis Syndrome in Patients with CLL and Coexisting Conditions Treated with Venetoclax-Obinutuzumab or ChlorambucilObinutuzumab: Results from the Randomized CLL14 Trial. Blood. 2019;134(Suppl1):4315-4315.
  • Rudakova A, Strugov V. The cost-effectiveness of treatment of relapsed/refractory chronic lymphocytic leukemia with a combination of venetoclax and rituximab. Journal of Modern Oncology. 2019;21(2):29-32.
  • Sharman J, Egyed M, Jurczak W, Skarbnik A, Pagel J, Flinn I et al. Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzumab for treatment-naive chronic lymphocytic leukaemia (ELEVATE-TN): a randomised, controlled, phase 3 trial. The Lancet. 2020;395(10232):12781291.
  • Da Cunha-Bang C, Agius R, Kater A, Levin M, Österborg A, Mattsson M et al. PreVent-ACaLL Short-term combined acalabrutinib and venetoclax treatment of newly diagnosed patients with CLL at high risk of infection and/or early treatment, who do not fulfil IWCLL treatment criteria for treatment. A randomized study with extensive immune phenotyping. Blood. 2019;134(Suppl1):4304-4304.
  • Cumbo C, Anelli L, Specchia G, Albano F. Monitoring of minimal residual disease (MRD) in chronic myeloid leukemia: Recent Advances. Cancer Management and Research, 2020;12:3175–3189. DOI: https://doi.org/10.2147/cmar.s232752
  • Ekinci O, Kizilkaya I. Imatinib mesylate in first-line treatment of chronic myeloid leukemia. Annals of Medical Research. 2019;26(9):1737.
  • Buyukasik Y. Use of second generationtyrosine kinase inhibitors for second-line treatment of chronic myeloid leukemiaafter Imatinib Failure. International Journal of Hematology and Oncology. 2011;21(2):4-9.
  • Vener C, Banzi R, Ambrogi F, Ferrero A, Saglio G, Pravettoni G et al. First-line imatinib vs second- and third-generation TKIs for chronic-phase CML: a systematic review and metaanalysis. Blood Advances. 2020;4(12):2723-2735.
  • Cumbo C, Anelli L, Specchia G, Albano F. Monitoring of minimal residual disease (MRD) in chronic myeloid leukemia: Recent Advances. Cancer Management and Research. 2020;12:3175–3189. DOI: https://doi.org/10.2147/cmar.s232752
  • Fakhri B, Andreadis C. The role of acalabrutinib in adults with chronic lymphocytic leukemia. Therapeutic Advances in Hematology. 2021;12:204062072199055.
  • Tariq S, Tariq S, Khan M, Azhar A, Baig M. Venetoclax in the Treatment of Chronic Lymphocytic Leukemia: Evidence, Expectations, and Future Prospects. Cureus. 2020;12(6).
  • Treon S, Meid K, Gustine J, Yang G, Xu L, Patterson C et al. Ibrutinib monotherapy produces long-term disease control in previously treated waldenstrom’s macroglobulinemia. Final report of the pivotal trial (nct01614821). Hematological Oncology. 2019;37:184-185.
  • Wierda WG, Kipps TJ, Mayer J, Stilgenbauer S, Williams CD, Hellmann A, Robak T, Furman RR, Hillmen P, Trneny M, et al. Ofatumumab as single- agent CD20 immunotherapy in fludarabine-refractory chronic lymphocytic leukemia. J Clin Oncol. 2010;28:1749–55.
  • Hillmen P, Robak T, Janssens A, Babu KG, Kloczko J, Grosicki S, Doubek M, Panagiotidis P, Kimby E, Schuh A, et al. Chlorambucil plus ofatumumab versus chlorambucil alone in previously untreated patients with chronic lymphocytic leukaemia (COMPLEMENT 1): a randomised, multicentre, open- label phase 3 trial. Lancet. 2015;385:1873–83.
  • Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370:1101–10.
  • Sehn LH, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, et al. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016;17:1081–93.
  • Usmani SZ, Weiss BM, Plesner T, Bahlis NJ, Belch A, Lonial S, Lokhorst HM, Voorhees PM, Richardson PG, Chari A, et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood. 2016;128:37–44.
  • Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, Spicka I, Hungria V, Munder M, Mateos MV, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754–66.
  • Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, Rabin N, Orlowski RZ, Komarnicki M, Suzuki K, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–31
  • Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, Walter- Croneck A, Moreau P, Mateos MV, Magen H, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–31.
  • Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, et al. Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin’s lymphoma. J Clin Oncol. 2012;30:2183–9.
  • Pro B, Advani R, Brice P, Bartlett NL, Rosenblatt JD, Illidge T, Matous J, Ramchandren R, Fanale M, Connors JM, et al. Brentuximab vedotin (SGN-35) in patients with relapsed or refractory systemic anaplastic large-cell lymphoma: results of a phase II study. J Clin Oncol. 2012;30:2190–6.
  • Moskowitz CH, Nademanee A, Masszi T, Agura E, Holowiecki J, Abidi MH, Chen AI, Stiff P, Gianni AM, Carella A, et al. 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. 2015;385:1853–62.
  • SehnL, Herrera AF, Flowers CR, Kamdar MK, McMillan A, Hertzberg M, Assouline S, et al. Polatuzumab Vedotin in Relapsed or Refractory Diffuse Large B-Cell Lymphoma, J Clin Oncol. 2020 Jan;38(2):155–165.
  • Couzin-Frankel J. Breakthrough of the year 2013. Cancer immunotherapy. Science. 2013;342:1432–3.
  • Mukherjee S. The emperor of all maladies. New York: Scribner; 2010 with the intention to eradicate the hematopoietic and immune systems of a patient with a curative for many patients with hematologic malignancies.
  • Pasquini MC, ZhuX. Current uses and outcomes of hematopoietic stem cell transplantation: CIBMTR summary slides. 2015. Available from:http://www.cibmtr.org.Accessed 2017.
  • Horowitz MM, Gale RP, Sondel PM, Goldman JM, Kersey J, Kolb HJ, Rimm AA, Ringden O, Rozman C, Speck B, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood. 1990;75:555–62.
  • Weiden PL, Flournoy N, Thomas ED, Prentice R, Fefer A, Buckner CD, Storb R. Antileukemic effect of graft-versushost disease in human recipients of allogeneic-marrow grafts. N Engl J Med. 1979;300:1068–73.
  • Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, Kamble R, Copelan E, de Lima M, Gupta V, et al. Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol. 2010;28:3730–8.
  • Lieskovsky YE, Donaldson SS, Torres MA, Wong RM, Amylon MD, Link MP, Agarwal R. High-dose therapy and autologous hematopoietic stem-cell transplantation for recurrent or refractory pediatric Hodgkin’s disease: results and prognostic indices. J Clin Oncol. 2004;22:4532–40.
  • Ali SA, Shi V, Maric I, Wang M, Stroncek DF, Rose JJ, Brudno JN, Stetler- Stevenson M, Feldman SA, Hansen BG, et al. T cells expressing an anti-B-cell- maturation-antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood. 2016. doi: https://doi.org/10.1182/blood-2016-04-711903.
  • Collins Jr RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R, Goodman SA, Wolff SN, Hu W, Verfaillie C, et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol. 1997;15:433–44.
  • Carella AM, Giralt S, Slavin S. Low intensity regimens with allogeneic hematopoietic stem cell transplantation as treatment of hematologic neoplasia. Haematologica.2000;85:304–13.
  • Gooley TA, Chien JW, Pergam SA, Hingorani S, Sorror ML, Boeckh M, Martin PJ, Sandmaier BM, Marr KA, Appelbaum FR, et al. Reduced mortality after allogeneic hematopoieticcell transplantation. N Engl J Med. 2010;363:2091–101.
  • Chang YJ, Xu LP, Wang Y, Zhang XH, Chen H, Chen YH, Wang FR, Han W, Sun YQ, Yan CH, et al. Controlled, randomized, open-label trial of risk- stratified corticosteroid prevention of acute graft-versus-host disease after haploidentical transplantation. J Clin Oncol. 2016;34:1855–63.
  • Bachireddy P, Burkhardt UE, Rajasagi M, Wu CJ. Haematological malignancies: at the forefront of immunotherapeutic innovation. Nat Rev Cancer. 2015;15:201–15
  • Whiteside TL. Immune cells in the tumor microenvironment. Mechanisms responsible for functional and signaling defects. Adv Exp Med Biol. 1998;451:167–71.
  • Andersen MH. The targeting of immunosuppressive mechanisms in hematological malignancies. Leukemia. 2014;28:1784–92.
  • Hills RK, Castaigne S, Appelbaum FR, Delaunay J, Petersdorf S, Othus M, Estey EH, Dombret H, Chevret S, Ifrah N, et al. Addition of gemtuzumabozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol. 2014;15:986–96.
  • Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gokbuget N, O’Brien S, Wang K, Wang T, et al. Inotuzumabozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med.2016;375:740–53.
  • Rogala B, Freyer CW, Ontiveros EP, Griffiths EA, Wang ES, Wetzler M. Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies. Expert Opin Biol Ther. 2015;15:895–908.
  • Fan G, Wang Z, Hao M, Li J. Bispecific antibodies and their applications. J Hematol Oncol. 2015;8:130.
  • Wu J, Fu J, Zhang M, Liu D. Blinatumomab: a bispecific T cell engager (BiTE) antibody against CD19/CD3 for refractory acute lymphoid leukemia. J Hematol Oncol. 2015;8:104.
  • Fan D, Li W, Yang Y, Zhang X, Zhang Q, Yan Y, Yang M, Wang J, Xiong D. Redirection of CD4+ and CD8+ T lymphocytes via an anti-CD3 x anti-CD19 bi-specific antibody combined with cytosine arabinoside and the efficient lysis of patientderived B-ALL cells. J Hematol Oncol. 2015;8:108.
  • Topp MS, Gokbuget N, Stein AS, Zugmaier G, O’Brien S, Bargou RC, Dombret H, Fielding AK, Heffner L, Larson RA, et al. Safety and activity of blinatumomab for adult patients with relapsed or refractory B-precursor acute lymphoblastic leukaemia: a multicentre, single-arm, phase 2 study. Lancet Oncol. 2015;16:57–66.
  • Zugmaier G, Gokbuget N, Klinger M, Viardot A, Stelljes M, Neumann S, Horst HA, Marks R, Faul C, Diedrich H, et al. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood. 2015;126:2578–84.
  • Topp MS, Kufer P, Gokbuget N, Goebeler M, Klinger M, Neumann S, Horst HA, Raff T, Viardot A, Schmid M, et al. Targeted therapy with the T-cell- engaging antibody blinatumomab of chemotherapy-refractory minimal residual disease in B-lineage acute lymphoblastic leukemia patients results in high response rate and prolonged leukemia-free survival. J Clin Oncol. 2011;29:2493–8.
  • Martinelli G, Dombret H, Chevallier P, Ottmann OG, Goekbuget N, Topp MS, Fielding AK, Sterling LR, Benjamin J, Stein AS. Complete molecular and hematologic response in adult patients with relapsed/refractory Philadelphia chromosomepositive B-precursor acute lymphoblastic leukemia following treatment with blinatumomab: results from a phase 2 single-arm, multicenter study (ALCANTARA) [abstract]. Blood. 2015;126:679.
  • Gokbuget N, Dombret H, Bonifacio M, Reichle A, Grauz C, Faul C, Diedrich H, Topp MS, Broggemann M, Horst HA, et al. Long-term outcomes after blinatumomab treatment: follow up of a phase 2 study in patients with minimal residual disease positive B-cell precursor acute lymphoblastic leukemia [abstract]. Blood. 2015;126:680.
  • Goebeler ME, Knop S, Viardot A, Kufer P, Topp MS, Einsele H, Noppeney R, Hess G, Kallert S, Mackensen A, et al. Bispecific T-cell engager (BiTE) antibody construct blinatumomab for the treatment of patients with relapsed/refractory non-Hodgkin lymphoma: final results from a phase I study. J Clin Oncol. 2016;34:1104–11.
  • Viardot A, Goebeler ME, Hess G, Neumann S, Pfreundschuh M, Adrian N, Zettl F, Libicher M, Sayehli C, Stieglmaier J, et al. Phase 2 study of the bispecific T-cell engager (BiTE) antibody blinatumomab in relapsed/ refractory diffuse large B-cell lymphoma. Blood. 2016;127:1410–6.
  • Maus MV, Grupp SA, Porter DL, June CH. Antibodymodified T cells: CARs take the front seat for hematologic malignancies. Blood. 2014;123:2625–35.
  • Maude SL, Teachey DT, Porter DL, Grupp SA. CD19targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood. 2015;125:4017–23.
  • Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, et al. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–28.
  • Brudno JN, Somerville RP, Shi V, Rose JJ, Halverson DC, Fowler DH, Gea- Banacloche JC, Pavletic SZ, Hickstein DD, Lu TL, et al. Allogeneic T cells that express an anti-CD19 chimeric antigen receptor induce remissions of B-cell malignancies that progress after allogeneic hematopoietic stemcell transplantation without causing graft-versus-host disease. J Clin Oncol. 2016;34:1112–21.
  • Park JH, Geyer MB, Brentjens RJ. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood. 2016;127:3312–20.
  • Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, Chew A, Gonzalez VE, Zheng Z, Lacey SF, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17.
  • Porter DL, Hwang WT, Frey NV, Lacey SF, Shaw PA, Loren AW, Bagg A, Marcucci KT, Shen A, Gonzalez V, et al. Chimeric antigen receptor T cells persist and induce sustained remissions in relapsed refractory chronic lymphocytic leukemia. Sci Transl Med. 2015;7:303ra139
  • Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol.2015;33:1974–82.
  • Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64.
  • Armand P. Immune checkpoint blockade in hematologic malignancies. Blood. 2015;125:3393–4000.
  • Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T, O’Donnell E, Chapuy B, Takeyama K, Neuberg D, Golub TR, et al. Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood. 2010;116:3268–77.
  • Roemer MG, Advani RH, Ligon AH, Natkunam Y, Redd RA, Homer H, Connelly CF, Sun HH, Daadi SE, Freeman GJ, et al. PD-L1 and PD-L2 genetic alterations define classical Hodgkin lymphoma and predict outcome. J Clin Oncol. 2016;34:2690–7.
  • Green MR, Rodig S, Juszczynski P, Ouyang J, Sinha P, O’Donnell E, Neuberg D, Shipp MA. Constitutive AP- 1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders:implications for targeted therapy. Clin Cancer Res.2012;18:1611–8.
  • Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, Armand P, Fanale M, Ratanatharathorn V, Kuruvilla J, et al. Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single- arm phase 2 trial. Lancet Oncol. 2016;17(9):1283–94.

Abstract Views: 93

PDF Views: 0




  • Challenges and Changing Trends in the Treatment of Haematological Cancers

Abstract Views: 93  |  PDF Views: 0

Authors

Abhay A. Bhave
Haematologist, Lilavati Hospital and Research Centre; Empire Haematology Oncology Centre, Bandra west, Mumbai, India
Sarang Waghmare
Fellow in Haematology, Lilavati Hospital and Research Centre, Bandra West, Mumbai, India
Nawal Kazi
Clinical Assistant, Empire Haematology Oncology Centre, Bandra west, Mumbai, India

Abstract


Chemotherapy and radiotherapy were the only weapons against cancer in the past. Research has opened up many vistas for treatment— different classes of drugs, targeted therapy, monoclonal antibodies and immunotherapy to name a few—that have become available in routine practice for the treatment of cancer. This was possible due to research grants/funds and pharma interest to detect new antigens with pharmacogenomics that identified targetable drugs against the antigens on the malignant cells. Disease eradication was the end point in the past that was achieved with great difficulty. With novel agents targeting different antigens through new drug routes and newer drug combinations, including “chemotherapy free” treatment, we seem to be doing better with less toxicity in treatment naïve and relapsed patients, who can now get another shot
at a disease-free survival or clinical remission. Currently many protocols utilise a combination of drugs- one belonging to the older generations and one novel agent (chemoimmunotherapy), a combination of new agents (chemotherapy free protocols), or a combination of subcutaneous and oral medications in the treatment of various malignancies. Futuristically, our aim is to use therapy which avoids / reduces hospitalization with a finite duration of therapy, making treatment cost-effective and more compliant leading to better and deeper malignant cell destruction. However, with the ever evolving and mutating
cancer cell for its survival, novel drugs will become old tomorrow and our protocols, combinations and sequencing of drugs will change over time with the advent of new drugs. The singular end point in cancer treatment today is better efficacy, safety and user-friendly protocols (oral or subcutaneous routes) that will achieve a deep response - undetectable minimal residual disease (uMRD) that will ultimately lead to treatment discontinuation. This in turn will improve compliance, prevent unnecessary toxicity and hopefully provide a functional cure. We are nearly there but we still do not routinely use the word
cure…yet! Hopefully someday.

Keywords


Malignancy, Chemotherapy, novel agents, chemoimmunotherapy, targeted therapy, monoclonal antibodies, uMRD

References