The development of targeted chemotherapy for CNS lymphoma?a pilot study of the IDARAM regimen

Moreton, Paul; Morgan, Gareth J.; Gilson, D.; Smith, Graeme; McVerry, B. A.; Davies, J. M.; Mackie, M. J.; Bolam, Simon; Jalihal, Sanjeev; Howard, Martin; Parapia, L. A.; Williams, Adrian; Child, J. A.

doi:10.1007/s00280-003-0737-2

Cited by 16 publications

(23 citation statements)

References 21 publications

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“…Neurotoxicity was low in the study population, with no patients developing grade 3/4 toxicity. It is unclear if the lack of mandatory radiotherapy was reflected in the outcomes of the present study: although the overall response rate was less than that originally reported by Moreton et al (), this may be a result of the introduction of standardized response criteria for neurological and systemic disease, as well as a greater use of PET‐CT and MRI imaging. Response criteria in the original report are not clearly described.…”

Section: Discussioncontrasting

confidence: 61%

“…We report one of the largest single‐centre cohorts treated for secondary CNS‐DLBCL, and the largest cohort of patients to be treated with IDARAM, which was specifically designed for the treatment of patients with primary and secondary CNSL (Moreton et al , ). We describe encouraging response rates and survival with the use of R‐IDARAM chemotherapy in those diagnosed early in the disease course, with a predictable and manageable toxicity profile.…”

Section: Discussionmentioning

confidence: 99%

“…In the original description of IDARAM, WBRT was given as consolidation as per protocol (40 Gy in 20 fractions), to patients with primary CNS lymphoma (PCNSL) or SCNSL (Moreton et al , ). There are limited data to confirm that this strategy improves outcomes in SCNSL.…”

Section: Discussionmentioning

confidence: 99%

“…The UK Central and Southern lymphoma group developed IDARAM (idarubicin, dexamethasone, Ara‐C and MTX) (Moreton et al , ), a rationally‐designed regimen for the treatment of CNS lymphoma, which combines drugs that can cross the blood‐brain barrier and includes idarubicin and high‐dose dexamethasone as well as CNS‐penetrating doses of IV MTX and Ara‐C, which were also given intrathecally. In 16 patients treated with IDARAM (without rituximab) with secondary B‐cell CNS lymphoma, the authors reported a CR rate of 75%, with durable CRs lasting 12–51 months at time of last follow‐up in 50% of patients (Moreton et al , ). On the basis of this encouraging data, this regimen was established as standard of care at our institution, with the addition of rituximab for patients with B‐cell lymphoma.…”

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confidence: 99%

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Treatment of diffuse large B‐cell lymphoma with secondary central nervous system involvement: encouraging efficacy using CNS‐penetrating R‐IDARAM chemotherapy

et al. 2015

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Diffuse large B-cell lymphoma with secondary involvement of the central nervous system (SCNS-DLBCL) is a rare condition carrying a poor prognosis. No optimal therapeutic regimen has been identified. We retrospectively analysed 23 patients with SCNS-DLBCL treated with R-IDARAM (rituximab 375 mg/m(2) IV day 1; methotrexate 12·5 mg by intrathecal injection day 1; idarubicin 10 mg/m(2) /day IV days 1 and 2; dexamethasone 100 mg/day IV infusion over 12 h days 1-3; cytosine arabinoside 1000 mg/m(2) /day IV over 1 h days 1 and 2; and methotrexate 2000 mg/m(2) IV over 2 h day 3. Ten out of 23 (44%) patients had CNS involvement at initial presentation ('new disease'), 10/23 (44%) had relapsed disease and 3/23 (13%) had primary refractory disease. 14/23 (61%) of patients responded - 6 (26%) complete response, 8 (35%) partial response. Grade 3-4 haematological toxicity was seen in all cycles, with no grade 3-4 or long-term neurological toxicity. Median follow-up for surviving patients was 49 months. At 2 years, estimated progression-free survival (PFS) was 39% and overall survival (OS) was 52%. Encouraging outcomes were reported in patients with new disease, with 5-year estimated PFS of 50% and OS 75%. R-IDARAM is a well-tolerated regimen with encouraging efficacy in patients with SCNS-DLBCL, although patients with relapsed or refractory disease continue to fare poorly.

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Section: Discussioncontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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Treatment of diffuse large B‐cell lymphoma with secondary central nervous system involvement: encouraging efficacy using CNS‐penetrating R‐IDARAM chemotherapy

et al. 2015

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“…The IDARAM regimen was found to be effective in seven patients with PCNSL by Moreton et al . . and was modified by Yilmaz et al .…”

Section: Discussionmentioning

confidence: 99%

Combined treatment of rituximab, idarubicin, dexamethasone, cytarabine, methotrexate with radiotherapy for primary central nervous system lymphoma

Zhao

Qian

Shen

et al. 2014

J Cellular Molecular Medi

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The overall response rates and long-term survival of primary central nervous system lymphoma (PCNSL) are still significantly inferior to the results achieved in similar subtypes of extranodal non-Hodgkin's lymphoma. It is clearly necessary to investigate new therapeutic methods on PCNSL. We encountered three patients histologically documented PCNSL as diffuse large B-cell lymphoma (DLBCL). They were treated with R-IDARAM which comprised rituximab, idarubicin, dexamethasone, cytarabine and methotrexate. Patient 1 received stereotactic brachytherapy (SBT) prior to chemotherapy performed with iodine-125 seeds (cumulative therapeutic dose 50 Gy). After six cycles of R-IDARAM at 3-weekly intervals, radiotherapy was applied at a dosage of 2000–4000 cGy in conventional schedule (180 or 200 cGy/day) to whole brain or spinal cord in all patients. Complete remission (CR) was achieved after first two cycles of R-IDARAM in all patients. All three patients remained in CR at the time of this report with a median duration of follow-up of 23 months (ranging from 13 to 41 months). Three patients have been alive for 41, 13, 16 months respectively until now. The patient with the longest survival time was the one given SBT prior to chemotherapy. This study suggests that R-IDARAM combining with radiotherapy maybe a high effective regimen in PCNSL patients especially those with primary central nervous system DLBCL. A comprehensive treatment combining internal radiotherapy by SBT, modified R-IDARAM and followed reduced external radiotherapy may be a new treatment concept for PCNSL with higher efficiency and lower toxicity.

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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

Olivier¹,

Clavert

Lacotte‐Thierry³

et al. 2014

American J Hematol

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Treatment of primary central nervous system lymphoma (PCNSL) in elderly patients remains unsatisfactory. To develop a new high-dose methotrexate (HD-MTX)-based regimen including idarubicin, a phase 1 multicenter dose escalation study was conducted to determine the maximum-tolerated dose (MTD) of idarubicin. Thirty-five immunocompetent patients with PCNSL were enrolled. The median age was 65 years (range, 60-70 years). MTX and vindesine (VDS) were given at the fixed dose of 3 g/m 2 (6-hr intravenous [IV]) and 3 mg/m 2 IV on day 1, respectively. Prednisolone (PRED) was given at the fixed dose of 60 mg/m 2 (IV or orally) on days 1-5. Idarubicin was escalated in increments of 2 mg/m 2 with doses ranging from 12-18 mg/m 2 IV on day 1. Treatment was repeated three times every 3 weeks. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia for more than 7 days, thrombocytopenia grade 4 or nonhaematological toxicity more than grade 2. The MTD of idarubicin was reached at 16 mg/m 2 . At this level, the main haematological toxicities were thrombocytopenia grade 4: 5% and neutropenia grade 3 or 4 (52%); the main nonhaematological toxicities were grade 3 or 4 infectious disease (5%) and grade 2 renal failure (9%). For the study population, median overall and progression-free survival were 19 and 13 months, respectively. Our study suggests that the MTD of idarubicin in combination with HD-MTX, VDS, and PRED, should be 16 mg/m 2 . Further studies will be necessary to challenge a standard treatment in elderly patients with PCNSL.

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The development of targeted chemotherapy for CNS lymphoma?a pilot study of the IDARAM regimen

Abstract: This study suggests that IDARAM is an effective regimen in both PCNSL and SCNSL and is suitable for further development and evaluation.

Cited by 16 publications

References 21 publications

Treatment of diffuse large B‐cell lymphoma with secondary central nervous system involvement: encouraging efficacy using CNS‐penetrating R‐IDARAM chemotherapy

Treatment of diffuse large B‐cell lymphoma with secondary central nervous system involvement: encouraging efficacy using CNS‐penetrating R‐IDARAM chemotherapy

Combined treatment of rituximab, idarubicin, dexamethasone, cytarabine, methotrexate with radiotherapy for primary central nervous system lymphoma

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

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