Letter to the Editor
Central Nervous System Multiple Myeloma Alessandro Gozzetti, Alfonso Cerase, Monica Bocchia Clinical Lymphoma, Myeloma & Leukemia, Vol. 15, No. 6, e133 ª 2015 Elsevier Inc. All rights reserved.
Dear Sir:
We read with interest the article by Abdallah and colleagues1 in which they describe clinical and biological data about 35 patients with a central nervous system involvement of myeloma (CNSMM). Median survival was 4 months. The authors stated aggressiveness of the disease, with particular attention to inefficacy of bone marrow transplantation and novel agents, in that they do not cross the bloodebrain barrier (BBB). Although we agree on the aggressiveness of the disease, we do not about inefficacy of bone marrow transplant and novel agents. In a recent study not cited by the authors2 we reported on 50 patients with intracranial multiple myeloma: osteoduraledural multiple myeloma (OD-MM) involvement was present in 38 of 50 (76%) patients including 3 patients with only dural involvement, and CNS-MM in 12 of 50 (24%) patients. New therapies (bortezomib, lenalidomide, thalidomide) were used in 35 patients and 15 patients received old treatments. Twenty-five of 50 patients obtained a complete remission or a very good partial remission (CRþVGPR). Median overall survival (OS) for CNS-MM was 6 months, and for OD-MM 25 months. OS for IC-MM patients treated with new agents was 25 months versus 8 months for patients treated with old agents. In our study, improved OS and progressionfree survival were predicted by response (CRþVGPR), patients who received stem cell autotransplant, and treatment with novel agents. Poor survival was present for patients with b2-microglobulin > 5.5 mmol/L and better survival for patients who achieved CRþVGPR. Cytogenetics was not a prognostic factor.
Hematology, University of Siena, Italy Submitted: May 24, 2014; Accepted: Oct 27, 2014; Epub: Oct 31, 2014 Address for correspondence: Alessandro Gozzetti, MD, PhD, Division of Hematology, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, Viale Bracci 16, 53100 Siena, Italy Fax: þ39-0577586185; e-mail contact: [email protected]
2152-2650/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clml.2014.10.004
In conclusion, different from the study by Abdallah et al,1 we saw a better outcome for patients who received autotransplant and novel agents. Three CNS-MM patients were treated with new agents and autologous bone marrow transplant (median follow-up, 12 months) and only 1 patient was treated with old drugs (follow-up, 23 months). It is notable that all of these new drugs do not seem to cross the BBB, even though just a few cases have been reported with thalidomide efficacy in CNS-MM where penetration through the BBB had been demonstrated.3-6 An interesting and fascinating theory could be that meningism inflammation or angiogenesis (as seen in glioblastomas)7 can allow increased vascular permeability resulting in the deterioration of the BBB, allowing some of these more efficient new drugs to pass through it. Additionally a recent phase I trial in which bortezomib was used in glioblastoma patients seems to confirm this.8 Finally, at a more recent follow-up, 1 of our patients (treated with bortezomib- dexamethasone and radiotherapy), was still alive at 50 months from diagnosis.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Abdallah AO, Atrash S, Shahid Z, et al. Patterns of central nervous system involvement in relapsed and refrectory multiple myeloma. Clin Lymphoma Myeloma Leuk 2014; 14:211-4. 2. Gozzetti A, Cerase A, Lotti F, et al. Extramedullary intracranial localizations of multiple myeloma and treatment with novel agents: a retrospective survey of 50 patients. Cancer 2012; 118:1574-84. 3. Cerase A, Tarantino A, Gozzetti A, et al. Intracranial involvement in plasmacytomas and multiple myeloma: a pictorial essay. Neuroradiology 2008; 50:665-74. 4. Vicari P, Ribas C, Sampaio M, et al. Can thalidomide be effective to treat plasma cell leptomeningeal infiltration? Eur J Haematol 2003; 70:198-9. 5. Yutaka H, Mariko Y, Shinichiro O, et al. Thalidomide for the treatment of leptomeningeal multiple myeloma. Eur J Haematol 2006; 76:358-9. 6. Schwartz R, Davidson T. Pharmacology, pharmacokinetics and practical applications of bortezomib. Oncology 2004; 18:14-21. 7. de Groot J, Milano V. Improving the prognosis for patients with glioblastoma: the rationale for targeting Src. J Neurooncol 2009; 95:151-63. 8. Phuphanich S, Supko JG, Carson KA, et al. Phase I clinical trial of bortezomib in adults with recurrent malignant glioma. J Neurooncol 2010; 100:95-103.
Clinical Lymphoma, Myeloma & Leukemia June 2015
- e133
Central Nervous System Multiple Myeloma Alessandro Gozzetti, Alfonso Cerase, Monica Bocchia Clinical Lymphoma, Myeloma & Leukemia, Vol. 15, No. 6, e133 ª 2015 Elsevier Inc. All rights reserved.
Dear Sir:
We read with interest the article by Abdallah and colleagues1 in which they describe clinical and biological data about 35 patients with a central nervous system involvement of myeloma (CNSMM). Median survival was 4 months. The authors stated aggressiveness of the disease, with particular attention to inefficacy of bone marrow transplantation and novel agents, in that they do not cross the bloodebrain barrier (BBB). Although we agree on the aggressiveness of the disease, we do not about inefficacy of bone marrow transplant and novel agents. In a recent study not cited by the authors2 we reported on 50 patients with intracranial multiple myeloma: osteoduraledural multiple myeloma (OD-MM) involvement was present in 38 of 50 (76%) patients including 3 patients with only dural involvement, and CNS-MM in 12 of 50 (24%) patients. New therapies (bortezomib, lenalidomide, thalidomide) were used in 35 patients and 15 patients received old treatments. Twenty-five of 50 patients obtained a complete remission or a very good partial remission (CRþVGPR). Median overall survival (OS) for CNS-MM was 6 months, and for OD-MM 25 months. OS for IC-MM patients treated with new agents was 25 months versus 8 months for patients treated with old agents. In our study, improved OS and progressionfree survival were predicted by response (CRþVGPR), patients who received stem cell autotransplant, and treatment with novel agents. Poor survival was present for patients with b2-microglobulin > 5.5 mmol/L and better survival for patients who achieved CRþVGPR. Cytogenetics was not a prognostic factor.
Hematology, University of Siena, Italy Submitted: May 24, 2014; Accepted: Oct 27, 2014; Epub: Oct 31, 2014 Address for correspondence: Alessandro Gozzetti, MD, PhD, Division of Hematology, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, Viale Bracci 16, 53100 Siena, Italy Fax: þ39-0577586185; e-mail contact: [email protected]
2152-2650/$ - see frontmatter ª 2015 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.clml.2014.10.004
In conclusion, different from the study by Abdallah et al,1 we saw a better outcome for patients who received autotransplant and novel agents. Three CNS-MM patients were treated with new agents and autologous bone marrow transplant (median follow-up, 12 months) and only 1 patient was treated with old drugs (follow-up, 23 months). It is notable that all of these new drugs do not seem to cross the BBB, even though just a few cases have been reported with thalidomide efficacy in CNS-MM where penetration through the BBB had been demonstrated.3-6 An interesting and fascinating theory could be that meningism inflammation or angiogenesis (as seen in glioblastomas)7 can allow increased vascular permeability resulting in the deterioration of the BBB, allowing some of these more efficient new drugs to pass through it. Additionally a recent phase I trial in which bortezomib was used in glioblastoma patients seems to confirm this.8 Finally, at a more recent follow-up, 1 of our patients (treated with bortezomib- dexamethasone and radiotherapy), was still alive at 50 months from diagnosis.
Disclosure The authors have stated that they have no conflicts of interest.
References 1. Abdallah AO, Atrash S, Shahid Z, et al. Patterns of central nervous system involvement in relapsed and refrectory multiple myeloma. Clin Lymphoma Myeloma Leuk 2014; 14:211-4. 2. Gozzetti A, Cerase A, Lotti F, et al. Extramedullary intracranial localizations of multiple myeloma and treatment with novel agents: a retrospective survey of 50 patients. Cancer 2012; 118:1574-84. 3. Cerase A, Tarantino A, Gozzetti A, et al. Intracranial involvement in plasmacytomas and multiple myeloma: a pictorial essay. Neuroradiology 2008; 50:665-74. 4. Vicari P, Ribas C, Sampaio M, et al. Can thalidomide be effective to treat plasma cell leptomeningeal infiltration? Eur J Haematol 2003; 70:198-9. 5. Yutaka H, Mariko Y, Shinichiro O, et al. Thalidomide for the treatment of leptomeningeal multiple myeloma. Eur J Haematol 2006; 76:358-9. 6. Schwartz R, Davidson T. Pharmacology, pharmacokinetics and practical applications of bortezomib. Oncology 2004; 18:14-21. 7. de Groot J, Milano V. Improving the prognosis for patients with glioblastoma: the rationale for targeting Src. J Neurooncol 2009; 95:151-63. 8. Phuphanich S, Supko JG, Carson KA, et al. Phase I clinical trial of bortezomib in adults with recurrent malignant glioma. J Neurooncol 2010; 100:95-103.
Clinical Lymphoma, Myeloma & Leukemia June 2015
- e133
