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08.08.2018 | Original Article

Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma

verfasst von: Jonathan Farhi, Kamel Laribi, Corentin Orvain, Jean-François Hamel, Mélanie Mercier, Aurélien Sutra Del Galy, Aline Clavert, Marie-Christine Rousselet, Aline Tanguy-Schmidt, Mathilde Hunault-Berger, Marie-Pierre Moles-Moreau

Erschienen in: Annals of Hematology | Ausgabe 12/2018

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Abstract

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7–73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3–60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2–46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate > 75% were associated with increased OS (p = 0.006 and p = 0.003, respectively) and PFS (p = 0.003 and p = 0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥ 8, were associated with decreased OS and PFS (p = 0.02 and p = 0.04, respectively). A high MSKCC score was associated with decreased OS (p = 0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p = 0.02 and p = 0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials.

Hoang-Xuan K, Bessell E, Bromberg J, Hottinger AF, Preusser M, Rudà R, Schlegel U, Siegal T, Soussain C, Abacioglu U, Cassoux N, Deckert M, Dirven CMF, Ferreri AJM, Graus F, Henriksson R, Herrlinger U, Taphoorn M, Soffietti R, Weller M (2015) Diagnosis and treatment of primary CNS lymphoma in immunocompetent patients: guidelines from the European Association for Neuro-Oncology. Lancet Oncol 16:e322–e332CrossRefPubMed

O’Neill BP, Decker PA, Tieu C, Cerhan JR (2013) The changing incidence of primary central nervous system lymphoma is driven primarily by the changing incidence in young and middle-aged men and differs from time trends in systemic diffuse large B-cell non-Hodgkin’s lymphoma. Am J Hematol 88:997–1000. https://doi.org/10.1002/ajh.23551 CrossRefPubMedPubMedCentral

Deckert M, Engert A, Brück W, Ferreri AJM, Finke J, Illerhaus G, Klapper W, Korfel A, Küppers R, Maarouf M, Montesinos-Rongen M, Paulus W, Schlegel U, Lassmann H, Wiestler OD, Siebert R, DeAngelis LM (2011) Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma. Leukemia 25:1797–1807. https://doi.org/10.1038/leu.2011.169 CrossRefPubMed

Camilleri-Broët S, Crinière E, Broët P et al (2006) A uniform activated B-cell-like immunophenotype might explain the poor prognosis of primary central nervous system lymphomas: analysis of 83 cases. Blood 107:190–196. https://doi.org/10.1182/blood-2005-03-1024 CrossRefPubMed

Kasenda B, Ferreri AJM, Marturano E, Forst D, Bromberg J, Ghesquieres H, Ferlay C, Blay JY, Hoang-Xuan K, Pulczynski EJ, Fosså A, Okoshi Y, Chiba S, Fritsch K, Omuro A, O'Neill BP, Bairey O, Schandelmaier S, Gloy V, Bhatnagar N, Haug S, Rahner S, Batchelor TT, Illerhaus G, Briel M (2015) First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL)--a systematic review and individual patient data meta-analysis. Ann Oncol 26:1305–1313. https://doi.org/10.1093/annonc/mdv076 CrossRefPubMedPubMedCentral

Roth P, Hoang-Xuan K (2014) Challenges in the treatment of elderly patients with primary central nervous system lymphoma. Curr Opin Neurol 27:697–701. https://doi.org/10.1097/WCO.0000000000000145 CrossRefPubMed

Ferreri AJM, Blay J-Y, Reni M, Pasini F, Spina M, Ambrosetti A, Calderoni A, Rossi A, Vavassori V, Conconi A, Devizzi L, Berger F, Ponzoni M, Borisch B, Tinguely M, Cerati M, Milani M, Orvieto E, Sanchez J, Chevreau C, Dell’Oro S, Zucca E, Cavalli F (2003) Prognostic scoring system for primary CNS lymphomas: the international extranodal lymphoma study group experience. J Clin Oncol 21:266–272CrossRefPubMed

Abrey LE, Ben-Porat L, Panageas KS, Yahalom J, Berkey B, Curran W, Schultz C, Leibel S, Nelson D, Mehta M, DeAngelis LM (2006) Primary central nervous system lymphoma: the Memorial Sloan-Kettering Cancer Center prognostic model. J Clin Oncol 24:5711–5715. https://doi.org/10.1200/JCO.2006.08.2941 CrossRefPubMed

Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 40:373–383CrossRefPubMed

10.

Miller MD, Paradis CF, Houck PR, Mazumdar S, Stack JA, Rifai AH, Mulsant B, Reynolds CF III (1992) Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res 41:237–248CrossRefPubMed

11.

Salvi F, Miller MD, Grilli A, Giorgi R, Towers AL, Morichi V, Spazzafumo L, Mancinelli L, Espinosa E, Rappelli A, DessÃ-Fulgheri P (2008) A manual of guidelines to score the modified cumulative illness rating scale and its validation in acute hospitalized elderly patients. J Am Geriatr Soc 56:1926–1931. https://doi.org/10.1111/j.1532-5415.2008.01935.x CrossRefPubMed

12.

Bellera CA, Rainfray M, Mathoulin-Pélissier S et al (2012) Screening older cancer patients: first evaluation of the G-8 geriatric screening tool. Ann Oncol 23:2166–2172. https://doi.org/10.1093/annonc/mdr587 CrossRefPubMed

13.

Hryniuk WM, Goodyear M (1990) The calculation of received dose intensity. J Clin Oncol 8:1935–1937CrossRefPubMed

14.

Fridrik MA, Greil R, Hausmaninger H et al (1997) Randomized open label phase III trial of CEOP/IMVP-Dexa alternating chemotherapy and filgrastim versus CEOP/IMVP-Dexa alternating chemotherapy for aggressive non-Hodgkin’s lymphoma (NHL). A multicenter trial by the Austrian Working Group for Medical Tumor Therapy. Ann Hematol 75:135–140CrossRefPubMed

15.

Abrey LE (2005) Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 23:5034–5043. https://doi.org/10.1200/JCO.2005.13.524 CrossRefPubMed

16.

National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 Published: May 28, 2009 (v4.03: June 14, 2010)

17.

Gavrilovic IT, Hormigo A, Yahalom J, DeAngelis LM, Abrey LE (2006) Long-term follow-up of high-dose methotrexate-based therapy with and without whole brain irradiation for newly diagnosed primary CNS lymphoma. J Clin Oncol 24:4570–4574. https://doi.org/10.1200/JCO.2006.06.6910 CrossRefPubMed

18.

Desablens B, Gardembas M, Delwail V et al (1999) Primary CNS lymphomas: long term results of the GOELAMS LCP88 trial with a focus on neurological complications among 152 patients. Ann Oncol 10(Suppl 3):40 (abstract)

19.

Poortmans PMP, Kluin-Nelemans HC, Haaxma-Reiche H, van’t Veer M, Hansen M, Soubeyran P, Taphoorn M, Thomas J, van den Bent M, Fickers M, van Imhoff G, Rozewicz C, Teodorovic I, van Glabbeke M (2003) High-dose methotrexate-based chemotherapy followed by consolidating radiotherapy in non-AIDS-related primary central nervous system lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962. J Clin Oncol 21:4483–4488. https://doi.org/10.1200/JCO.2003.03.108 CrossRefPubMed

20.

Lyman GH, Crawford J, Tomita D, Whittaker S, Dale DC (2015) Changing patterns of chemotherapy relative dose intensity and supportive care for aggressive B-cell non-Hodgkin lymphoma. Leuk Lymphoma 57:1–8. https://doi.org/10.3109/10428194.2015.1045894 CrossRef

21.

Olivier G, Clavert A, Lacotte-Thierry L, Gardembas M, Escoffre-Barbe M, Brion A, Cumin I, Legouffe E, Solal-Celigny P, Chabin M, Ingrand P, Colombat P, Delwail V (2014) A phase 1 dose escalation study of idarubicin combined with methotrexate, vindesine, and prednisolone for untreated elderly patients with primary central nervous system lymphoma. The GOELAMS LCP 99 trial. Am J Hematol 89:1024–1029. https://doi.org/10.1002/ajh.23812 CrossRefPubMed

22.

Omuro A, Chinot O, Taillandier L, Ghesquieres H, Soussain C, Delwail V, Lamy T, Gressin R, Choquet S, Soubeyran P, Huchet A, Benouaich-Amiel A, Lebouvier-Sadot S, Gyan E, Touitou V, Barrié M, del Rio MS, Gonzalez-Aguilar A, Houillier C, Delgadillo D, Lacomblez L, Tanguy ML, Hoang-Xuan K (2015) Methotrexate and temozolomide versus methotrexate, procarbazine, vincristine, and cytarabine for primary CNS lymphoma in an elderly population: an intergroup ANOCEF-GOELAMS randomised phase 2 trial. Lancet Haematol 2:e251–e259CrossRefPubMed

23.

Fritsch K, Kasenda B, Schorb E, Hau P, Bloehdorn J, Möhle R, Löw S, Binder M, Atta J, Keller U, Wolf HH, Krause SW, Heß G, Naumann R, Sasse S, Hirt C, Lamprecht M, Martens U, Morgner A, Panse J, Frickhofen N, Röth A, Hader C, Deckert M, Fricker H, Ihorst G, Finke J, Illerhaus G (2017) High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study). Leukemia 31:846–852. https://doi.org/10.1038/leu.2016.334 CrossRefPubMed

24.

Wildiers H, Reiser M (2011) Relative dose intensity of chemotherapy and its impact on outcomes in patients with early breast cancer or aggressive lymphoma. Crit Rev Oncol Hematol 77:221–240. https://doi.org/10.1016/j.critrevonc.2010.02.002 CrossRefPubMed

25.

Joerger M, Huitema ADR, Illerhaus G, Ferreri AJM (2012) Rational administration schedule for high-dose methotrexate in patients with primary central nervous system lymphoma. Leuk Lymphoma 53:1867–1875. https://doi.org/10.3109/10428194.2012.676177 CrossRefPubMed

26.

Ferreri AJM, Guerra E, Regazzi M, Pasini F, Ambrosetti A, Pivnik A, Gubkin A, Calderoni A, Spina M, Brandes A, Ferrarese F, Rognone A, Govi S, Dell'Oro S, Locatelli M, Villa E, Reni M (2004) Area under the curve of methotrexate and creatinine clearance are outcome-determining factors in primary CNS lymphomas. Br J Cancer 90:353–358. https://doi.org/10.1038/sj.bjc.6601472 CrossRefPubMedPubMedCentral

27.

Ferreri AJM, Reni M, Foppoli M, Martelli M, Pangalis GA, Frezzato M, Cabras MG, Fabbri A, Corazzelli G, Ilariucci F, Rossi G, Soffietti R, Stelitano C, Vallisa D, Zaja F, Zoppegno L, Aondio GM, Avvisati G, Balzarotti M, Brandes AA, Fajardo J, Gomez H, Guarini A, Pinotti G, Rigacci L, Uhlmann C, Picozzi P, Vezzulli P, Ponzoni M, Zucca E, Caligaris-Cappio F, Cavalli F (2009) High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial. Lancet 374:1512–1520. https://doi.org/10.1016/S0140-6736(09)61416-1 CrossRefPubMed

28.

Coiffier B, Lepage E, Briere J et al (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med 346:235–242. https://doi.org/10.1056/NEJMoa011795 CrossRefPubMed

29.

Siegal T (2014) Primary central nervous system lymphoma: current state of anti-CD20 therapy and appraisal of reported response criteria. J Clin Neurosci 21:709–715. https://doi.org/10.1016/j.jocn.2014.02.002 CrossRefPubMed

30.

Shah GD, Yahalom J, Correa DD, Lai RK, Raizer JJ, Schiff D, LaRocca R, Grant B, DeAngelis LM, Abrey LE (2007) Combined immunochemotherapy with reduced whole-brain radiotherapy for newly diagnosed primary CNS lymphoma. J Clin Oncol 25:4730–4735. https://doi.org/10.1200/JCO.2007.12.5062 CrossRefPubMed

31.

Birnbaum T, Stadler EA, von Baumgarten L, Straube A (2012) Rituximab significantly improves complete response rate in patients with primary CNS lymphoma. J Neuro-Oncol 109:285–291. https://doi.org/10.1007/s11060-012-0891-7 CrossRef

32.

Gregory G, Arumugaswamy A, Leung T, Chan KL, Abikhair M, Tam C, Bajel A, Cher L, Grigg A, Ritchie D, Opat S (2013) Rituximab is associated with improved survival for aggressive B cell CNS lymphoma. Neuro-Oncology 15:1068–1073. https://doi.org/10.1093/neuonc/not032 CrossRefPubMedPubMedCentral

33.

Kansara R, Shenkier TN, Connors JM, Sehn LH, Savage KJ, Gerrie AS, Villa D (2015) Rituximab with high-dose methotrexate in primary central nervous system lymphoma. Am J Hematol 90:1149–1154. https://doi.org/10.1002/ajh.24204 CrossRefPubMed

34.

Holdhoff M, Ambady P, Abdelaziz A, Sarai G, Bonekamp D, Blakeley J, Grossman SA, Ye X (2014) High-dose methotrexate with or without rituximab in newly diagnosed primary CNS lymphoma. Neurology 83:235–239CrossRefPubMedPubMedCentral

35.

Madle M, Krämer I, Lehners N, Schwarzbich M, Wuchter P, Herfarth K, Egerer G, Ho AD, Witzens-Harig M (2015) The influence of rituximab, high-dose therapy followed by autologous stem cell transplantation, and age in patients with primary CNS lymphoma. Ann Hematol 94:1853–1857. https://doi.org/10.1007/s00277-015-2470-4 CrossRefPubMed

36.

Chamberlain MC, Johnston SK (2010) High-dose methotrexate and rituximab with deferred radiotherapy for newly diagnosed primary B-cell CNS lymphoma. Neuro-Oncology 12:736–744. https://doi.org/10.1093/neuonc/noq011 CrossRefPubMedPubMedCentral

37.

Fritsch K, Kasenda B, Hader C, Nikkhah G, Prinz M, Haug V, Haug S, Ihorst G, Finke J, Illerhaus G (2011) Immunochemotherapy with rituximab, methotrexate, procarbazine, and lomustine for primary CNS lymphoma (PCNSL) in the elderly. Ann Oncol 22:2080–2085. https://doi.org/10.1093/annonc/mdq712 CrossRefPubMed

38.

Rubenstein JL, Hsi ED, Johnson JL, Jung SH, Nakashima MO, Grant B, Cheson BD, Kaplan LD (2013) Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202). J Clin Oncol 31:3061–3068. https://doi.org/10.1200/JCO.2012.46.9957 CrossRefPubMedPubMedCentral

39.

Ferreri AJM, Cwynarski K, Pulczynski E, Ponzoni M, Deckert M, Politi LS, Torri V, Fox CP, Rosée PL, Schorb E, Ambrosetti A, Roth A, Hemmaway C, Ferrari A, Linton KM, Rudà R, Binder M, Pukrop T, Balzarotti M, Fabbri A, Johnson P, Gørløv JS, Hess G, Panse J, Pisani F, Tucci A, Stilgenbauer S, Hertenstein B, Keller U, Krause SW, Levis A, Schmoll HJ, Cavalli F, Finke J, Reni M, Zucca E, Illerhaus G (2016) Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematol 3:e217–e227. https://doi.org/10.1016/S2352-3026(16)00036-3 CrossRefPubMed

40.

Bromberg J, Issa S, Bukanina K et al (2017) Effect of rituximab in primary central nervous system lymphoma - results of the Randomized Phase III HOVON 105/ALLG NHL 24 Study. Blood 130:582–582

41.

Song Y, Wen Y, Xue W, Zhang Y, Zhang M (2017) Effect of rituximab on primary central nervous system lymphoma: a meta-analysis. Int J Hematol 106:612–621. https://doi.org/10.1007/s12185-017-2316-z CrossRefPubMed

42.

Terret C, Albrand G, Rainfray M, Soubeyran P (2015) Impact of comorbidities on the treatment of non-Hodgkin’s lymphoma: a systematic review. Expert Rev Hematol 8:329–341. https://doi.org/10.1586/17474086.2015.1024650 CrossRefPubMed

43.

Extermann M, Boler I, Reich RR, Lyman GH, Brown RH, DeFelice J, Levine RM, Lubiner ET, Reyes P, Schreiber FJ III, Balducci L (2012) Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score. Cancer 118:3377–3386. https://doi.org/10.1002/cncr.26646 CrossRefPubMed

44.

Hurria A, Togawa K, Mohile SG, Owusu C, Klepin HD, Gross CP, Lichtman SM, Gajra A, Bhatia S, Katheria V, Klapper S, Hansen K, Ramani R, Lachs M, Wong FL, Tew WP (2011) Predicting chemotherapy toxicity in older adults with cancer: a prospective multicenter study. J Clin Oncol 29:3457–3465. https://doi.org/10.1200/JCO.2011.34.7625 CrossRefPubMedPubMedCentral

45.

Aaldriks AA, Maartense E, le Cessie S, Giltay EJ, Verlaan HACM, van der Geest LGM, Kloosterman-Boele WM, Peters-Dijkshoorn MT, Blansjaar BA, van Schaick HW, Nortier JWR (2011) Predictive value of geriatric assessment for patients older than 70 years, treated with chemotherapy. Crit Rev Oncol Hematol 79:205–212. https://doi.org/10.1016/j.critrevonc.2010.05.009 CrossRefPubMed

46.

Kanesvaran R, Li H, Koo K-N, Poon D (2011) Analysis of prognostic factors of comprehensive geriatric assessment and development of a clinical scoring system in elderly Asian patients with cancer. J Clin Oncol 29:3620–3627. https://doi.org/10.1200/JCO.2010.32.0796 CrossRefPubMed

47.

Soubeyran P, Bellera C, Goyard J, Heitz D, Curé H, Rousselot H, Albrand G, Servent V, Jean OS, van Praagh I, Kurtz JE, Périn S, Verhaeghe JL, Terret C, Desauw C, Girre V, Mertens C, Mathoulin-Pélissier S, Rainfray M (2014) Screening for vulnerability in older cancer patients: the ONCODAGE Prospective Multicenter Cohort Study. PLoS One 9:e115060. https://doi.org/10.1371/journal.pone.0115060 CrossRefPubMedPubMedCentral

48.

Decoster L, Van Puyvelde K, Mohile S et al (2015) Screening tools for multidimensional health problems warranting a geriatric assessment in older cancer patients: an update on SIOG recommendations†. Ann Oncol 26:288–300. https://doi.org/10.1093/annonc/mdu210 CrossRefPubMed

49.

Dubruille S, Libert Y, Roos M, Vandenbossche S, Collard A, Meuleman N, Maerevoet M, Etienne AM, Reynaert C, Razavi D, Bron D (2015) Identification of clinical parameters predictive of one-year survival using two geriatric tools in clinically fit older patients with hematological malignancies: major impact of cognition. J Geriatr Oncol 6:362–369. https://doi.org/10.1016/j.jgo.2015.07.006 CrossRefPubMed

Titel: Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma
verfasst von: Jonathan Farhi
Kamel Laribi
Corentin Orvain
Jean-François Hamel
Mélanie Mercier
Aurélien Sutra Del Galy
Aline Clavert
Marie-Christine Rousselet
Aline Tanguy-Schmidt
Mathilde Hunault-Berger
Marie-Pierre Moles-Moreau
Publikationsdatum: 08.08.2018
Verlag: Springer Berlin Heidelberg
Erschienen in: Annals of Hematology / Ausgabe 12/2018
Print ISSN: 0939-5555
Elektronische ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-018-3468-5

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Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma

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