401
Views
5
CrossRef citations to date
0
Altmetric
Review

Management of elderly and unfit patients with chronic lymphocytic leukemia

, , , , , , , & show all
Pages 1165-1175 | Received 18 Jul 2016, Accepted 26 Oct 2016, Published online: 21 Nov 2016

References

  • Balducci L, Dolan D. Chronic lymphocytic leukemia in the elderly: epidemiology and proposed patient-related approach. Cancer Control. 2015;22(4 Suppl):3–6.
  • Tam CS, O’Brien S, Wierda W, et al. Long-term results of the fludarabine, cyclophosphamide, and rituximab regimen as initial therapy of chronic lymphocytic leukemia. Blood. 2008;112(4):975–980.
  • Fischer K, Cramer P, Busch R, et al. Bendamustine in combination with rituximab for previously untreated patients with chronic lymphocytic leukemia: a multicenter phase II trial of the German chronic lymphocytic leukemia study group. J Clin Oncol. 2012;30(26):3209–3216.
  • Eichhorst B, Fink AM, Bahlo J, et al. First-line chemoimmunotherapy with bendamustine and rituximab versus fludarabine, cyclophosphamide, and rituximab in patients with advanced chronic lymphocytic leukaemia (CLL10): an international, open-label, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2016;17:928–942.
  • Goede V, Cramer P, Busch R, et al. Interactions between comorbidity and treatment of chronic lymphocytic leukemia: results of German chronic lymphocytic leukemia study group trials. Haematologica. 2014;99(6):1095–1100.
  • Abrisqueta P, Pereira A, Rozman C, et al. Improving survival in patients with chronic lymphocytic leukemia (1980-2008): the hospital clinic of Barcelona experience. Blood. 2009;114(10):2044–2050.
  • Baumann T, Delgado J, Santacruz R, et al. Chronic lymphocytic leukemia in the elderly: clinico-bilogical features, outcomes, and proposal of a prognostic model. Haematologica. 2014;99(10):1599–1604.
  • Brenner H, Gondos A, Pulte D. Trends in long-term survival of patients with chronic lymphocytic leukemia from the 1980s to the early 21st century. Blood. 2008;111(10):4916–4921.
  • Wierda WG, O’Brien S, Wang X, et al. Characteristics associated with important clinical end points in patients with chronic lymphocytic leukemia at initial treatment. J Clin Oncol. 2009;27(10):1637–1643.
  • Shanafelt TD, Rabe KG, Kay NE, et al. Age at diagnosis and the utility of prognostic testing in patients with chronic lymphocytic leukemia. Cancer. 2010;116(20):4777–4787.
  • Mauro FR, Foa R, Giannarelli D, et al. Clinical characteristics and outcome of young chronic lymphocytic leukemia patients: a single institution study of 204 cases. Blood. 1999;94(2):448–454.
  • Gentile M, Mauro FR, Rossi D, et al. Italian external and multicentric validation of the MD Anderson cancer center nomogram and prognostic index for chronic lymphocytic leukaemia patients: analysis of 1502 cases. Br J Haematol. 2014;167(2):224–232.
  • Hillmen P, Gribben JG, Follows GA, et al. Rituximab plus chlorambucil as first-line treatment for chronic lymphocytic leukemia: final analysis of an open-label phase II study. J Clin Oncol. 2014;32(12):1236–1241.
  • Foa R, Del Giudice I, Cuneo A, et al. Chlorambucil plus rituximab with or without maintenance rituximab as first-line treatment for elderly chronic lymphocytic leukemia patients. Am J Hematol. 2014;89(5):480–486.
  • Goede V, Fischer K, Busch R, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101–1110.
  • Hillmen P, Robak T, Janssens 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(9980):1873–1883.
  • Badoux XC, Keating MJ, Wen S, et al. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood. 2011;118(13):3489–3498.
  • Strati P, Keating MJ, Wierda WG, et al. Lenalidomide induces long-lasting responses in elderly patients with chronic lymphocytic leukemia. Blood. 2013;122(5):734–737.
  • O’Brien S, Furman RR, Coutre SE, et al. Ibrutinib as initial therapy for elderly patients with chronic lymphocytic leukaemia or small lymphocytic lymphoma: an open-label, multicentre, phase 1b/2 trial. Lancet Oncol. 2014;15(1):48–58.
  • Burger JA, Tedeschi A, Barr PM, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425–2437.
  • Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997–1007.
  • O’Brien SM, Lamanna N, Kipps TJ, et al. A phase 2 study of idelalisib plus rituximab in treatment-naive older patients with chronic lymphocytic leukemia. Blood. 2015;126(25):2686–2694.
  • Jagger A, Shimojima Y, Goronzy JJ, et al. Regulatory T cells and the immune aging process: a mini-review. Gerontology. 2014;60(2):130–137.
  • Balducci L. Myelosuppression and its consequences in elderly patients with cancer. Oncology. 2003;17(Suppl 11):27–32.
  • Read WL, Tierney RM, Page NC, et al. Differential prognostic impact of comorbidity. J Clin Oncol. 2004;2(15):3099–3103.
  • Thurmes P, Call T, Slager S, et al. Comorbid conditions and survival in unselected, newly diagnosed patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2008;49(1):49–56.
  • Satram-Hoang S, Reyes C, Hoang KQ, et al. Treatment practice in the elderly patient with chronic lymphocytic leukemia-analysis of the combined SEER and medicare database. Ann Hematol. 2014;93(8):1335–1344.
  • Charlson M, Szatrowski TP, Peterson J, et al. Validation of a combined comorbidity index. J Clin Epidemiol. 1994;47(11):1245–1251.
  • Miller MD, Paradis CF, Houck PR, et al. Rating chronic medical illness burden in geropsychiatric practice and research: application of the cumulative illness rating scale. Psychiat Res. 1992;41(3):237–248.
  • NCCN Cancer Network. Clinical Practice Guidelines in Oncology v3.2016 (NCCN Guidelines®) - Chronic Lymphocytic Leukemia/Small Lymphocytic lymphoma. Available from: https://www.nccn.org/
  • Wierda WG, O’Brien S, Wang X, et al. Prognostic nomogram and index for overall survival in previously untreated patients with chronic lymphocytic leukemia. Blood. 2007;109(11):4679–4685.
  • Pflug N, Bahlo J, Shanafelt TD, et al. Development of a comprehensive prognostic index for patients with chronic lymphocytic leukemia. Blood. 2014;124(1):49–62.
  • Kutsch N, Bahlo J, Byrd JC, et al. The International Prognostic Index for patients with CLL (CLL-IPI): an international meta-analysis. 2015 ASCO Annual Meeting. J Clin Oncol. 2015;33(suppl; abstr 7002).
  • Parikh SA, Shanafelt TD. Prognostic factors and risk stratification in chronic lymphocytic leukemia. Semin Oncol. 2016;43(2):233–240.
  • Naeim A, Aapro M, Subbarao R, et al. Supportive care considerations for older adults with cancer. J Clin Oncol. 2014;32(24):2627–2634.
  • Eichhorst BF, Busch R, Stilgenbauer S, et al. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 2009;114(16):3382–3391.
  • International CLL-IPI working group. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data. Lancet Oncol. 2016;17(6):779–790.
  • Wang L, Baser O, Kutikova L, et al. The impact of primary prophylaxis with granulocyte colony-stimulating factors on febrile neutropenia during chemotherapy: a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer. 2015;23(11):3131–3140.
  • Aapro MS, Bohlius J, Cameron DA, et al. 2010 update of EORTC guidelines for the use of granulocyte-colony stimulating factor to reduce the incidence of chemotherapy-induced febrile neutropenia in adult patients with lymphoproliferative disorders and solid tumours. Eur J Cancer. 2011;47(1):8–32.
  • Kuderer NM, Dale DC, Crawford J, et al. Mortality, morbidity, and cost associated with febrile neutropenia in adult cancer patients. Cancer. 2006;106(10):2258–2266.
  • Morrison VA. Infectious complications of chronic lymphocytic leukaemia: pathogenesis, spectrum of infection, preventive approaches. Best Pract Res Cl Ha. 2010;23(1):145–153.
  • Anemia BL. fatigue and aging. Transfus Clin Biol. 2010;17(5–6):375–381.
  • Shanafelt TD, Drake MT, Maurer MJ, et al. D insufficiency and prognosis in chronic lymphocytic leukemia. Blood. 2011;117(5):1492–1498.
  • Molica S1, Digiesi G, Antenucci A, et al. Vitamin D insufficiency predicts time to first treatment (TFT) in early chronic lymphocytic leukemia (CLL). Leuk Res. 2012;36(4):443–447.
  • Weinstein JR, Anderson S. The aging kidney: physiological changes. Adv Chronic Kidney Dis. 2010;17(4):302–307.
  • Cheson BD, Brugger W, Damaj G, et al. Optimal use of bendamustine in hematologic disorders: treatment recommendations from an international consensus panel-an update. Leuk Lymphoma. 2016;57(4):766–782.
  • Chanan-Khan A, Cramer P, Demirkan F, et al. Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study. Lancet Oncol. 2015;17(2):200–211.
  • Foon KA, Mehta D, Lentzsch S, et al. Long-term results of chemoimmunotherapy with low-dose fludarabine, cyclophosphamide and high-dose rituximab as initial treatment for patients with chronic lymphocytic leukemia. Blood. 2012;119(13):3184–3185.
  • Dartigeas C, Van Den Neste E, Berthou C, et al. Evaluating abbreviated induction with fludarabine, cyclophosphamide, and dose-dense rituximab in elderly patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2015 Sep 28;1–7. [ Epub ahead of print].
  • Lew TE, Cheah CY, Carney DA, et al. Dose-reduced fludarabine, cyclophosphamide and rituximab is well tolerated in older patients with chronic lymphocytic leukemia and has preserved therapeutic efficacy. Leuk Lymphoma. 2016;57(5):1044–1053.
  • Kovacs G, Bahlo J, Kluth S, et al. Prognostic impact and risk factors of reducing prescribed doses of Fludarabine, Cyclophosphamide and Rituximab (FCR) during frontline treatment of Chronic Lymphocytic Leukemia (CLL). Blood. 2015;126:4156.
  • Shanafelt TD, Lin T, Geyer SM, et al. Pentostatin, cyclophosphamide, and rituximab regimen in older patients with chronic lymphocytic leukemia. Cancer. 2007;109(11):2291–2298.
  • Michallet AS, Aktan M, Schuh A, et al. Rituximab in combination with bendamustine or chlorambucil for the treatment of chronic lymphocytic leukemia: Primary results from the randomized phase IIIb MaBLe study. iwCLL Abstracts. 2015:178.
  • Stilgenbauer S, Ilhan O, Woszczyk D, et al. Safety and efficacy of obinutuzumab plus bendamustine in previously untreated patients with chronic lymphocytic leukemia: subgroup analysis of the green study. Blood. 2015;126:493.
  • Woyach JA, Ruppert AS, Rai K, et al. Impact of age on outcomes after initial therapy with chemotherapy and different chemoimmunotherapy regimens in patients with chronic lymphocytic leukemia: results of sequential cancer and leukemia group B studies. J Clin Oncol. 2013;31(4):440–447.
  • Goede V, Fischer K, Busch R, et al. Chemoimmunotherapy with GA101 plus chlorambucil in patients with chronic lymphocytic leukemia and comorbidity: results of the CLL11 (BO21004) safety run-in. Leukemia. 2013;27(5):1172–1174.
  • Balakrishnan K, Peluso M, Fu M, et al. The phosphoinositide-3-kinase (PI3K)-delta and gamma inhibitor, IPI-145 (Duvelisib), overcomes signals from the PI3K/AKT/S6 pathway and promotes apoptosis in CLL. Leukemia. 2015;29(9):1811–1822.
  • Byrd JC, Harrington B, O’Brien S, et al. Acalabrutinib (ACP-196) in relapsed chronic lymphocytic leukemia. New Engl J Med. 2016;374(4):323–332.
  • Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. New Engl J Med. 2013;369(1):32–42.
  • Byrd JC, Furman RR, Coutre SE, et al. Three-year follow-up of treatment-naive and previously treated patients with CLL and SLL receiving single-agent ibrutinib. Blood. 2015;125(16):2497–2506.
  • Byrd JC, Brown JR, O’Brien S, et al. Ibrutinib versus ofatumumab in previously treated chronic lymphoid leukemia. N Engl J Med. 2014;371(3):213–223.
  • Thompson PA, Stingo F, Keating MJ, et al. Outcomes of patients with chronic lymphocytic leukemia treated with first-line idelalisib plus rituximab after cessation of treatment for toxicity. Cancer. 2016 May 16;122:2505–2511. Epub ahead of print. DOI: 10.1002/cncr.30069
  • Lampson BL, Kasar SN, Matos TR, et al. Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity. Blood. 2016 Jul 14;128(2):195–203.
  • Coutre SE, Barrientos JC, Brown JR, et al. Management of adverse events associated with idelalisib treatment: expert panel opinion. LeukLymphoma. 2015;56(10):2779–2786.
  • Louie CY, DiMaio MA, Matsukuma KE, et al. Idelalisib-associated enterocolitis: clinicopathologicfeatures and distinction from other enterocolitides. Am J Surg Pathol. 2015;39(12):1653–1660.
  • Weidner AS, Panarelli NC, Geyer JT, et al. Idelalisib-associated colitis: histologic findings in 14 patients. Am J Surg Pathol. 2015;39(12):1661–1667.
  • Patton DT, Garden OA, Pearce WP, et al. Cutting edge: the phosphoinositide 3-kinase p110 delta is critical for the function of CD4+CD25+Foxp3+ regulatory T cells. J Immunol. 2006;177(10):6598–6602.
  • Ramsdell F, Ziegler SF. FOXP3 and scurfy: how it all began. Nat Rev Immunol. 2014;14(5):343–349.
  • PRAC concludes review of Zydelig and issues updated recommendations for use. European Medicine Agency. 2016; EMA/459461/2016.  Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2016/07/WC500209936.pdf
  • Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with Venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):311–322.
  • Ma S Bd, Seymour JF, Danielle M.B, et al. Deep and durable responses following venetoclax (ABT-199/GDC-0199) combined with rituximab in patients with relapsed/refractory chronic lymphocytic leukemia: results from a phase 1b study. Blood. 2015;126:830.
  • Fischer K, Bishop H, Mark Dixon, et al. Results of the safety run-in phase of CLL14 (BO25323): a prospective, open-label, multicenter randomized phase III trial to compare the efficacy and safety of Obinutuzumab and Venetoclax (GDC-0199/ABT-199) with obinutuzumab and chlorambucil in patients with previously untreated CLL and coexisting medical conditions. Blood. 2015;126:496.
  • Seymour JF. Effective mitigation of tumor lysis syndrome with gradual venetoclax dose ramp, prophylaxis, and monitoring in patients with chronic lymphocytic leukemia. Ann Hematol. 2016;95(8):1361–1362.
  • Stilgenbauer S, Zenz T, Winkler D, et al. Subcutaneous alemtuzumab in fludarabine-refractory chronic lymphocytic leukemia: clinical results and prognostic marker analyses from the CLL2H study of the German chronic lymphocytic leukemia study group. J Clin Oncol. 2009;27(24):3994–4001.
  • Pettitt AR, Jackson R, Carruthers S, et al. Alemtuzumab in combination with methylprednisolone is a highly effective induction regimen for patients with chronic lymphocytic leukemia and deletion of TP53: fina l results of the national cancer research institute CLL206 trial. J Clin Oncol. 2012;30(14):1647–1655.
  • Stilgenbauer S, Ilhan O, Woszczyk D. Outcome of ibrutinib treatment by baseline genetic features in patients with relapsed or refractory CLL/SLL with del17p in the resonate-17 study. Blood. 2015;126:493.
  • Sharman Jp Cs, Furman RR, Coutre S. E., et al. Second interim analysis of a phase 3 study of idelalisib (ZYDELIG) plus rituximab (R) for relapsed chronic lymphocytic leukemia (CLL): efficacy analysis in patient subpopulations with Del(17p) and other adverse prognostic factors. Blood. 2014;124:33.
  • Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016;17(6):768–778.
  • Eichhorst B, Robak T, Montserrat E, et al. Chronic lymphocytic leukaemia: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015;26(Suppl 5):78–84.
  • Rossi D, Terzi-di-Bergamo L, De Paoli L, et al. Molecular prediction of durable remission after first-line fludarabine-cyclophosphamide-rituximab in chronic lymphocytic leukemia. Blood. 2015;126(16):1921–1924.
  • Fischer K, Bahlo J, Fink AM, et al. Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood. 2016;127(2):208–215.
  • Thompson PA, Tam CS, O’Brien SM, et al. Fludarabine, cyclophosphamide, and rituximab treatment achieves long-term disease-free survival in IGHV-mutated chronic lymphocytic leukemia. Blood. 2016;127(3):303–309.
  • Herling CD, Klaumünzer M, Krings Rocha C, et al. Complex karyotypes, KRAS and POT1 mutations impact outcome in CLL after chlorambucil based chemo- or chemoimmunotherapy. Blood. 2016 Jul 21;128(3):395–404.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.