Clinical UM Guideline

 

Subject: Romidepsin (Istodax®)
Guideline #:  CG-DRUG-51 Publish Date:    06/06/2018
Status: Reviewed Last Review Date:    05/03/2018

Description

This document addresses the clinical uses of romidepsin (Istodax, Celgene Corporation, Summit, NJ).

Clinical Indications

Medically Necessary:

Romidepsin is considered medically necessary for the following indications:

  1. Individuals with relapsed or refractory T-cell lymphoma or leukemia following at least one prior systemic therapy; or
  2. Individuals with mycosis fungoides or Sézary Syndrome.

Not Medically Necessary:

Romidepsin is considered not medically necessary when the medically necessary criteria are not met and for all other indications.

Coding

The following codes for treatments and procedures applicable to this guideline are included below for informational purposes. Inclusion or exclusion of a procedure, diagnosis or device code(s) does not constitute or imply member coverage or provider reimbursement policy. Please refer to the member's contract benefits in effect at the time of service to determine coverage or non-coverage of these services as it applies to an individual member.

HCPCS

 

J9315

Injection, romidepsin, 1 mg [Istodax]

 

 

ICD-10 Diagnosis

 

C84.00-C84.09

Mycosis fungoides

C84.10-C84.19

Sézary disease

C84.40-C84.49

Peripheral T-cell lymphoma, not classified

C84.60-C84.79

Anaplastic large cell lymphoma

C84.A0-C84.A9

Cutaneous T-cell lymphoma, unspecified

C86.2

Enteropathy-type (intestinal) T-cell lymphoma

C86.5

Angioimmunoblastic T-cell lymphoma

C86.6

Primary cutaneous CD30-positive T-cell proliferations

Z85.72

Personal history of non-Hodgkin lymphomas

Discussion/General Information

Lymphoma is a cancer that starts in cells that are part of the body's immune system. One of the most common forms of T-cell lymphoma is cutaneous T-cell lymphoma. T-cell lymphomas account for approximately 15% of all non-Hodgkin lymphoma in the United States. Peripheral T-cell lymphoma consists of a group of rare and usually aggressive (fast-growing) non-Hodgkin lymphomas that develop from mature T-cells.

Romidepsin was initially approved by the United States Food and Drug Administration (FDA) in 2009. Romidepsin is a histone deacetylase (HDAC) inhibitor indicated for the treatment of cutaneous T-cell lymphoma in individuals who have received at least one prior systemic therapy. In addition to the FDA labeled indications, the National Comprehensive Cancer Network® has given 2A off-label recommendations for romidepsin for individuals with mycosis fungoides and Sézary Syndrome.

In 2009, Piekarz and colleagues reported on a phase II trial in which evaluated the efficacy and safety of romidepsin in 71 participants with T-cell lymphoma. This particular study was limited to those individuals with the subtypes of mycosis fungoides or Sézary Syndrome. The initial cohort of participants (n=27) had received no more than 2 systemic cytotoxic chemotherapy regimens. The protocol was then expanded to include participants who had received more than two prior cytotoxic chemotherapy regimens. This additional cohort included 44 participants. There were no limits on other types of prior treatments and those included topical treatments, biologic agents, and radiation therapy. Participants received a median of four cycles of romidepsin. Of the initial 27 participants who had received no more than 2 prior cytotoxic regimens, 3 participants achieved a complete response, 8 participants achieved a partial response with an overall response rate of 41% (95% CI [confidence interval], 22% to 61%). For the entire cohort population (n=71), the overall response rate was 34% (95% CI, 23% to 46%). Toxicities included fatigue, nausea and vomiting, anorexia, leukopenia, granulocytopenia, lymphopenia, thrombocytopenia, anemia, and transient elevations of liver function tests. There were 3 deaths during the study and 3 other deaths occurred within 30 days of removal from the study. The median duration of response was 13.7 months.

A 2010 study by Whittaker and colleagues reported on 96 participants with cutaneous T-cell lymphoma who received romidepsin after receiving prior systemic therapies. The objective response rate was 34% with 6 participants achieving complete response. Response to romidepsin was observed regardless of the stage of the disease and was found to be active in all disease compartments including blood, skin and lymph nodes. The median duration of objective response was 15 months. Some of the most common reported toxicities included nausea, fatigue, lethargy, vomiting, anorexia, diarrhea, headache, thrombocytopenia, and anemia. These side effects were reported to be mild.

In 2011, the FDA expanded the drug label to include the indication of peripheral T-cell lymphoma in individuals who have received at least one prior therapy.

In a phase II trial by Piekarz and colleagues (2011), 47 participants with peripheral T-cell lymphoma were enrolled to evaluate the efficacy and long-term safety of romidepsin and who had not received more than 2 cytotoxic chemotherapy regimens. The trial was later amended and expanded to include participants with peripheral T-cell lymphoma who had received any number of prior treatment regimens. Two participants were later determined to be ineligible, so 45 participants were assessed for response to romidepsin. Following a median of three cycles and nine doses, eight participants achieved complete response and nine participants achieved partial response with an overall response rate of 38% (95% CI, 24% to 53%). Toxicities included fatigue, nausea and vomiting, anorexia, leukopenia, granulocytopenia, lymphopenia, thrombocytopenia, and anemia. The participants who achieved complete response had a median duration of response of 29.7 months while those with partial response had a median duration of response of 5.2 months.

A phase II study by Coiffier and colleagues (2012) reported on 130 participants with relapsed or refractory peripheral T-cell lymphoma who received romidepsin. The median number of prior systemic therapies was two. Using an independent review committee, the objective response rate was 25% (33 of 130), of which 19 participants achieved complete response. The study investigator findings were similar with an objective response rate of 29% (38 of 130) with 21 participants achieving complete response. For those participants who were refractory to their most recent prior therapy, 14 of 49 responded. The median duration of response was 17 months. Similar to previous studies, the most common toxicities included nausea, fatigue, thrombocytopenia, vomiting and diarrhea. These side effects were reported as mild to moderate in severity.

The 2016 FDA drug label lists the following warnings and precautions:

There are no listed contraindications and the most common adverse reactions were neutropenia, lymphopenia, thrombocytopenia, infections, nausea, fatigue, vomiting, anorexia, anemia, and ECG T-wave changes.

Definitions

Complete response: The disappearance of all signs of cancer as a result of treatment; also called complete remission; does not indicate the cancer has been cured.

Disease-free survival: In cancer, the length of time after primary treatment for a cancer ends that the individual survives without any signs or symptoms of that cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

Line of therapy:

First-line therapy: The first or primary treatment for the diagnosis. This may include surgery, chemotherapy, radiation therapy or a combination of these therapies.
Second-line therapy: Treatment given when initial treatment (first-line therapy) is not effective or there is disease progression.
Third-line therapy: Treatment given when both initial (first-line therapy) and subsequent treatment (second-line therapy) are not effective or there is disease progression.

Mycosis fungoides: A sub-type of cutaneous T-cell lymphoma in which tumor cells invade the skin causing reddening (erythroderma) and/or plaques. There may also be involvement of lymph nodes, blood, and internal organs.

non-Hodgkin's Lymphoma: A group of malignant solid tumors of lymphoid tissues.

Partial response: A decrease in the size of a tumor, or in the amount of cancer in the body, resulting from treatment; also called partial remission.

Progression free survival: The time from random assignment in a clinical trial to disease progression.

Progressive disease: Cancer that is growing, spreading, or getting worse; also called disease progression.

Refractory disease: Illness or disease that does not respond to treatment.

Relapsed disease: The worsening of an oncologic disease after a period of improvement or remission.

Sézary Syndrome: A sub-type of cutaneous T-cell lymphoma characterized by itching and redness with T cell leukemia whose cells clonally match those invading the skin. Sézary Syndrome has historically been more difficult to treat than mycosis fungoides.

References

Peer Reviewed Publications:

  1. Bates SE, Eisch R, Ling A, et al. Romidepsin in peripheral and cutaneous T-cell lymphoma: mechanistic implications from clinical and correlative data. Br J Haematol. 2015; 170(1):96-109.
  2. Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012; 30(6):631-636.
  3. Maruyama D, Tobinai K, Ogura M, et al. Romidepsin in Japanese patients with relapsed or refractory peripheral T-cell lymphoma: a phase I/II and pharmacokinetics study. Int J Hematol. 2017; 106(5):655-665.
  4. Piekarz RL, Frye R, Turner M, et al. Phase II multi-institutional trial of the histone deacetylase inhibitor romidepsin as monotherapy for patients with cutaneous T-cell lymphoma. J Clin Oncol. 2009; 27(32):5410-5417.
  5. Piekarz RL, Frye R, Prince HM, et al. Phase 2 trial of romidepsin in patients with peripheral T-cell lymphoma. Blood. 2011; 117(22):5827-5834.
  6. Whittaker SJ, Demierre MF, Kim EJ, et al. Final results from a multicenter, international, pivotal study of romidepsin in refractory cutaneous T-cell lymphoma. J Clin Oncol. 2010; 28(29):4485-4491.

Government Agency, Medical Society, and Other Authoritative Publications:

  1. Istodax [Product Information], Summit, NJ. Celgene Corporation; July 2016. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022393s014lbl.pdf. Accessed on March 29, 2018.
  2. National Comprehensive Cancer Network®. NCCN Drugs & Biologic Compendium™ (electronic version). For additional information visit the NCCN website: http://www.nccn.org. Accessed on March 29, 2018.
  3. NCCN Clinical Practice Guidelines in Oncology®. © 2018 National Comprehensive Cancer Network, Inc. For additional information visit the NCCN website: http://www.nccn.org. Accessed on March 29, 2018.
    • T-Cell Lymphomas (V.3.2018). Revised February 22, 2018.
  4. Romidepsin Monograph. Lexicomp® Online, American Hospital Formulary Service® (AHFS®) Online, Hudson, Ohio, Lexi-Comp., Inc. Last revised March 8, 2017. Accessed on March 29, 2018.
  5. Romidepsin (systemic). In: DrugPoints System [electronic version]. Truven Health Analytics. Greenwood Village, CO. Updated February 15, 2018. Available at: http://www.micromedexsolutions.com. Accessed on March 29, 2018.
Websites for Additional Information
  1. American Cancer Society. Available at: http://www.cancer.org/. Accessed on March 29, 2018.
  2. National Cancer Institute (NCI). Available at: http://www.cancer.gov. Accessed on March 29, 2018.
Index

Istodax
Lymphoma
Romidepsin

The use of specific product names is illustrative only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available.

History

Status

Date

Action

Reviewed

05/03/2018

Medical Policy & Technology Assessment Committee (MPTAC) review.

Reviewed

05/02/2018

Hematology/Oncology Subcommittee review. The document header wording updated from “Current Effective Date” to “Publish Date.” Updated References section.

Reviewed

05/04/2017

MPTAC review.

Reviewed

05/03/2017

Hematology/Oncology Subcommittee review. Updated Description, Background/Overview and References sections.

New

05/05/2016

MPTAC review.

New

05/04/2016

Hematology/Oncology Subcommittee review. Initial document development.