The Effect of Rituximab, Cyclophosphamide, Vincristine, and Prednisolone (R-CVP) Chemotherapy in Patients with Ocular Adnexal Extranodal Marginal Zone B Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Sung Jin Park; Won Sik Lee; Jae Wook Yang

doi:10.3341/jkos.2013.54.8.1157

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Park, Lee, and Yang: The Effect of Rituximab, Cyclophosphamide, Vincristine, and Prednisolone (R-CVP) Chemotherapy in Patients with Ocular Adnexal Extranodal Marginal Zone B Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Original Article

J Korean Ophthalmol Soc 2013;54(8):1157-1164.

Published online: 7 September 2013

DOI: https://doi.org/10.3341/jkos.2013.54.8.1157

The Effect of Rituximab, Cyclophosphamide, Vincristine, and Prednisolone (R-CVP) Chemotherapy in Patients with Ocular Adnexal Extranodal Marginal Zone B Cell Lymphoma of the Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma

Sung Jin Park, MD¹, Won Sik Lee, MD, PhD³, Jae Wook Yang, MD, PhD^1,^2,

¹Department of Ophthalmology, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea

²Ocular Neovascular Disease Research Center, Busan, Korea

³Department of Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea

Address reprint requests to Jae Wook Yang, MD, PhD Department of Ophthalmology, Busan Paik Hospital #75 Bokji-ro, Busanjin-gu, Busan 614-735, Korea Tel: 82-51-890-8710, Fax: 82-51-890-6329, E-mail: oculoplasty@gmail.com

This study was presented as a narration at the 108th Annual Meeting of the Korean Ophthalmology Society 2012.

This study was supported by a grant from the Korea Healthcare Technology R&D Project, Ministry of Health and Welfare Affairs, Republic of Korea (Grant NO. HI12C0005).

Received 29 December 201226 March 2013 Accepted 25 June 2013

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

To report the effectiveness of rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP) combination chemotherapy in patients with ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (OAML).

Methods

R-CVP chemotherapy was performed in 7 patients (8 eyes) with a confirmed histopathological diagnosis of OAML from January 2012 to December 2012. A total of 6 cycles were administered at a 3-4 week interval and 2 cycles of rituximab were added at the third week. Response evaluation was performed 3 times, with the first evaluation 3 weeks after the third cycle, the second 3 weeks after the sixth cycle, and the last after the second rituximab cycle.

Results

In all 7 patients (8 eyes) with R-CVP, symptoms were improved, and the mass was markedly resolved based on orbit CT and MRI scan at first response evaluation. Clinically complete remission (CR) was achieved in 6 patients and par-tial response (PR) in 1 patient. At final response assessment, there was no detectable mass on orbit CT or MRI. There were no severe infections or hematologic adverse effects including neutropenia or decreased immunoglobulin during the follow-up period.

Conclusions

In OAML, R-CVP combination chemotherapy is considered an effective, safe and important therapeutic ap-proach, reducing the limitations of classic localized radiotherapy and combination chemotherapy and improving the re-mission rate.

Keywords: Ocular Adnexal MALT Lymphoma, Radiotherapy, R-CVP

References

1. Stefanovic A, Lossos IS. Extranodal marginal zone lymphoma of the ocular adnexa. Blood. 2009; 114:501–10.

2. Cho EY, Han JJ, Ree HJ. . Clinicopathologic analysis of ocular adnexal lymphomas: Extranodal marginal zone b-cell lymphoma constitutes the vast majority of ocular lymphomas among koreans and affects younger patients. Am J Hematol. 2003; 73:87–96.

3. Ko YH, Kim CW, Park CS. . REAL classification of malignant lymphomas in the Republic of Korea: incidence of recently recognized entities and changes in clinicopathologic features. Hemato- lymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American lymphoma. Cancer. 1998; 83:806–12.

4. Pittaluga S, Bijnens L, Teodorovic I. . Clinical analysis of 670 cases in two trials of the European Organization for the Research and Treatment of Cancer Lymphoma Cooperative Group subtyped according to the Revised European-American Classification of Lymphoid Neoplasms: a comparison with the Working Formulation. Blood. 1996; 87:4358–67.

5. Sweetenham JW, Smartt PF, Wilkins BS. . The clinical utility of the Revised European-American Lymphoma (R.E.A.L.) Classification: preliminary results of a prospective study in patients with non-Hodgkin's lymphoma from a single centre. Ann Oncol. 1999; 10:1121–4.

6. Yoon JS, Ma KT, Kim SJ. . Prognosis for patients in a Korean population with ocular adnexal lymphoproliferative lesions. Ophthal Plast Reconstr Surg. 2007; 23:94–9.

7. Cheson BD, Pfistner B, Juweid ME. . Revised response criteria for malignant lymphoma. J Clin Oncol. 2007; 25:579–86.

8. Lee SW, Suh CO, Kim GE. . Role of radiotherapy for primary orbital lymphoma. Am J Clin Oncol. 2002; 25:261–5.

9. Martinet S, Ozsahin M, Belkacemi Y. . Outcome and prog-nostic factors in orbital lymphoma: a Rare Cancer Network study on 90 consecutive patients treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2003; 55:892–8.

10. Raderer M, Streubel B, Woehrer S. . High relapse rate in patients with malt lymphoma warrants lifelong flow-up. High relapse rate in patients with malt lymphoma warrants lifelong flow-up. Clin Cancer Res. 2005; 11:3349–52.

11. Uno T, Isobe K, Shikama N. . Radiotherapy for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue originating in the ocular adnexa: a multiinstitutional, retro-spective review of 50 patients. Cancer. 2003; 98:865–71.

12. Coiffier B. Immunochemotherapy: the new standard in aggressive non-Hodgkin's lymphoma in the elderly. Semin Oncol. 2003; 30:(1 Suppl 2). 21–7.

13. Cheson BD, Horning SJ, Coiffier B. . Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999; 17:1244.

14. Nutting CM, Jenkins CD, Norton AJ. . Primary orbital lymphoma. Hematol J. 2002; 3:14–6.

15. Bairey O, Kremer I, Rakowsky E. . Orbital and adnexal in-volvement in systemic non-Hodgkin's lymphoma. Cancer. 1994; 73:2395–9.

16. Volpe NJ, Gausas RE. Optic nerve and orbital tumors. Neurosurg Clin N Am. 1999; 10:699–715, ix-x.

17. Ejima Y, Sasaki R, Okamoto Y. . Ocular adnexal mucosa-asso-ciated lymphoid tissue lymphoma treated with radiotherapy. Radiother Oncol. 2006; 78:6–9.

18. Coupland SE, White VA, Rootman J. . A TNM-based clinical staging system of ocular adnexal lymphomas. Arch Pathol Lab Med. 2009; 133:1262–7.

19. Decaudin D, de Cremoux P, Vincent-Salomon A. . Ocular ad-nexal lymphoma: a review of clinicopathologic features and treat-ment options. Blood. 2006; 108:1451–60.

20. Ben Simon GJ, Cheung N, McKelvie P. . Oral chlorambucil for extranodal, marginal zone, B-cell lymphoma of mucosa-associated lymphoid tissue of the orbit. Ophthalmology. 2006; 113:1209–13.

21. Lee JL, Kim MK, Lee KH. . Extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue-type of the orbit and ocular adnexa. Ann Hematol. 2005; 84:13–8.

22. Song EK, Kim SY, Kim TM. . Efficacy of chemotherapy as a first-line treatment in ocular adnexal extranodal marginal zone B-cell lymphoma. Annals of Oncology. 2008; 19:242–6.

23. Paik JS, Cho WK, Lee SE. . Ophthalmologic outcomes after chemotherapy and/or radiotherapy in non-conjunctival ocular ad-nexal MALT lymphoma. Ann Hematol. 2012; 91:1393–401.

24. Jakobiec FA, Knowles DM. An overview of ocular adnexal lym-phoid tumors. Trans Am Ophthalmol Soc. 1989; 87:420–42.

25. Knowles DM, Jakobiec FA, McNally L, Burke JS. Lymphoid hy-perplasia and malignant lymphoma occurring in the ocular adnexa (orbit, conjunctiva, and eyelids): a prospective multiparametric analysis of 108 cases during 1977 to 1987. Hum Pathol. 1990; 21:959–73.

26. Hainsworth JD, Litchy S, Burris HA 3rd. . Rituximab as first-line and maintenance therapy for patients with indolent non-hodgkin's lymphoma. J Clin Oncol. 2002; 20:4261–7.

27. McLaughlin P, Grillo-López AJ, Link BK. . Rituximab chi-meric anti-CD20 monoclonal antibody therapy for relapsed in-dolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol. 1998; 16:2825–33.

28. Coiffier B, Haioun C, Ketterer N. . Rituximab (anti-CD20 monoclonal antibody) for the treatment of patients with relapsing or refractory aggressive lymphoma: a multicenter phase II study. Blood. 1998; 92:1927–32.

29. Maloney DG, Grillo-López AJ, Bodkin DJ. . IDEC-C2B8: re-sults of a phase I multiple-dose trial in patients with relapsed non-Hodgkin's lymphoma. J Clin Oncol. 1997; 15:3266–74.

30. Hainsworth JD, Litchy S, Barton JH. . Single-agent rituximab as first-line and maintenance treatment for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol. 2003; 21:1746–51.

31. Huhn D, von Schilling C, Wilhelm M. . Rituximab therapy of patients with B-cell chronic lymphocytic leukemia. Blood. 2001; 98:1326–31.

32. Keating MJ, O'Brien S, Albitar M. Emerging information on the use of rituximab in chronic lymphocytic leukemia. Semin Oncol. 2002; 29:70–4.

Figure 1.

Right eye shows upper lid swelling, proptosis, conjunctival injection and chemosis (A, B). Upper lid swelling, proptosis, conjunctival injection and chemosis, medial gaze limitation in right eye have markedly decreased after R-CVP infusion (C, D).

Figure 2.

Coronal MRI scans show enhancing mass in medial aspect (involving conal/intraconal/extraconal spaces) of right orbit (postseptal location). (A) It extends to orbital apex, but there is no evidence of tumor invasion into right optic canal or intracranial extension. After R-CVP infusion, size and enhancement of known orbital MALT lymphoma in right postseptal medial area have moderately decreased. (B) In CT scans no enhancing mass was detected (figure not shown).

Figure 3.

Right eye shows proptosis, conjunctival injection and chemosis. Down and lateral gaze limitation of right eye is prominent (A, B). Proptosis, conjunctival injection and chemosis, down and lateral gaze limitation in right eye have markedly decreased after R-CVP infusion (C, D).

Figure 4.

Coronal CT scans show sharply defined high density mass with moderate homogenous enhancement in retro-bulbar space of right orbit (A). No evidence of adjacent bony erosion or intracranial extension. After R-CVP infusion, markedly decreased extent of homogenous enhancing mass in retrobulbar space of right orbit has seen (B).

Figure 5.

Both eyes show lower conjunctival injection and salmon patch appearance mass-like lesion (A, C). Lower conjunctival in-jection and chemosis in both eye have markedly decreased after R-CVP infusion. In CT and MRI scans, no visualization of discrete mass lesion in both orbits and periorbital (B, D).

Table 1.

Demographics and clinical characteristics in patients treated with R-CVP diagnosed with ocular adnexal MALT lymphoma

Case	Sex/ Age	Clinical menifestations	Laterality	Site (lesions)	Median period tween symptom rearance and fir nic visit (month)	Staging	Final response	Complications	Follow up (month)
1	M/39	Lower lid swelling Conjunctival injection	OS	Orbit	1	II	CR	Peripheral neuropathy (tingling sensation)	9
2	M/43	Proptosis， (3 mm)	OD	Eyelid	4	III	CR	URI Sx	7
		Upper lid swelling
		EOM limitation : -3 at medial
3	M/43	Proptosis， (5 mm) EOM limitation : -2 at down，-1 at lateral	OD	Eyelid	1	III	CR	Peripheral neuropathy (tingling sensation)	8
4	M/51	Lower lid swelling	OS	Orbit	1	II	CR	-	5
		Conjunctival injection
5	M/31	Lower conjunctival injection	OS	Orbit	3	II	CR	URI Sx	4
		Lower lid swelling
6	F/53	Upper lid drooping and swelling	OU	Conjunctiva	3	I	CR	-	6
7	M/47	Upper lid swelling	OD	Orbit	1	II	PR	-	3
		EOM limitation : -1.5 at up，
		-1 at medial

EOM = extraocular muscle; CR = complete remission; PR = partial remission; URI = upper respiratory infection.

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