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Oprelvekin (Neumega)

Number: 0855



Policy

Aetna considers oprelvekin (Neumega) medically necessary for prevention of thrombocytopenia in persons who are receiving myelosuppressive therapy for non-myeloid malignancies who are at high-risk of severe thrombocytopenia (i.e., platelet count less than 50,000 or previous thromobytopenia with prior chemotherapy).

Aetna considers oprelvekin experimental and investigational for all other indications including the following (not an all-inclusive list):

  • Dengue fever-associated thrombocytopenia
  • Hemophilia A
  • Menorrhagia
  • Peripheral vascular disease
  • von Willebrand disease
Background

Neumega (oprelvekin) is indicated for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in adult patients with nonmyeloid malignancies who are at high risk of severe thrombocytopenia.

The recommended dose of oprelvekin in adults without severe renal impairment is 50 µg/kg given once-daily (Wyeth, 2011).  The recommended dose of Neumega (oprelvekin) in adults with severe renal impairment (creatinine clearance less than 30 ml/min) is 25 µg/kg.

According to the product labeling, dosing should be initiated 6 to 24 hours after the completion of chemotherapy (Wyeth, 2011).  Platelet counts should be monitored periodically to assess the optimal duration of therapy.  Dosing should be continued until the post-nadir platelet count is greaterthan or equal to 50,000/µL.  The product labeling notes that, in controlled clinical trials, doses were administered in courses of 10 to 21 days.  The product labeling states that dosing beyond 21 days per treatment course is not recommended.

The product labeling states that treatment with oprelvekin should be discontinued at least 2 days before starting the next planned cycle of chemotherapy.

Dengue Fever-Associated Thrombocytopenia:

In a randomized, double-blind, placebo-control study, Suliman and colleagues (2014) evaluated the effectiveness of recombinant human (rh) interleukin (IL)-11 (oprelvekin) to increase platelets count in patients suffering from Dengue fever (DF). A total of 40 hospitalized patients suffering from Dengue fever (with platelets count less than 30,000/uL) were randomly categorized into 2 groups: (i) rhIL-11 (test) and (ii) distilled water (placebo) groups. The efficacy outcomes (as indicated by step up in platelets count at 48 hours) for the treatment group were compared with the outcomes for the placebo group. The data revealed that the increase in platelet response with rhIL-11, 1.5 mg subcutaneously is significantly more brisk than the placebo group. The platelets response in patients with severe thrombocytopenia was greater in the treatment group (50 %) at 48 hours as compared to the placebo group (20 %) (p = 0.047). Response rate was slightly greater among males (6/10, 60 %) than females (8/16, 50 %); moreover, 75 % female responders were in the placebo group, compared to 50 % male responders in the treatment group. The authors concluded that results of the study suggested that treatment of severe thrombocytopenia accompanying DF with rhIL-11 may be a useful therapeutic option.

Furthermore, an UpToDate review on “Prevention and treatment of dengue virus infection” (Rothman et al, 2015) does not mention interleukin-11/oprelvekin as a therapeutic option.

Hemophilia A and von Willebrand Disease:

Ragni et al (2013) noted that desmopressin (DDAVP) is the treatment of choice in those with mild von Willebrand disease (VWD), yet 20 % are unresponsive to DDAVP, and among the 80 % who respond, the response is transient, as endothelial stores are depleted after 3 days. These researchers conducted a single-center, phase II clinical trial to determine safety and effectiveness of recombinant interleukin-11 (rhIL-11, Neumega) in patients with VWD unresponsive or allergic to DDAVP, or mild or moderate hemophilia A (HA). Increases in VWF:RCo were observed by 48 hours after rhIL-11, with a 1.54-fold increase by day 4, 1.3-fold in VWD and 1.73-fold in HA. Similarly, by 48 hours, increases in VIII:C were observed, with a 1.65-fold increase by day 4, 1.86-fold in VWD and 1.48-fold in HA. Platelet VWFmRNA expression by quantitative PCR (qPCR) increased 0.81-fold but did not correlate with plasma VWF:Ag responses; rhIL-11 was well-tolerated, with grade 1 or less fluid retention, flushing, conjunctival erythema, except for transient grade 3 hyponatremia in 1 subject after excess fluid intake for diabetic hyperglycemia, which resolved with fluid restriction. The authors concluded that rhIL-11 increases VWF levels in 2 of 4 DDAVP-unresponsive or allergic VWD and F.VIII levels in 4 of 5 mild or moderate hemophilia A subjects, suggesting its potential use in treatment of these disorders.

UpToDate reviews on “Treatment of von Willebrand disease” (Rick, 2015) and “Treatment of hemophilia” (Hoots and Shapiro, 2015) do not mention interleukin-11/oprelvekin as a therapeutic option.

Menorrhagia:

Ragni et al (2011) stated that lack of effective treatment for menorrhagia is the greatest unmet healthcare need in women with VWD. These investigators conducted a single-center, phase II clinical trial to determine the safety and effectiveness of rhIL-11 given subcutaneously for up to 7 days during 6 consecutive menstrual cycles each in 7 women with mild VWD and menorrhagia refractory to hemostatic or hormonal agents. Recombinant IL-11 reduced menstrual bleeding severity as measured by pictorial blood assessment chart (PBAC) greater than or equal to 50 % (to less than 100) in 71 % of subjects, cycle severity greater than or equal to 50 % in 71 %, and bleeding duration greater than or equal to 2 days in 85 %, all p ≤ 0.01. After rhIL-11, plasma VWF:RCo increased 1.1-fold, but did not correlate with PBAC, r = 0.116, bleeding duration, r = 0.318, or cycle severity, r = -0.295, or high sensitivity C-reactive protein (hsCRP), r = -0.003, all p > 0.05. Platelet VWF mRNA expression by qPCR increased mean 4r-fold (1.0 to 13.5). The authors concluded thatrhIL-11 was well-tolerated with grade 1 or less fluid retention, flushing, conjunctival erythema, and local bruising; rhIL-11 reduces menorrhagia safely and warrants further study.

Peripheral Vascular Disease:

Aitsebaomo et al (2011) examined the role of rhIL-11 on in-vivo mobilization of CD34(+)/vascular endothelial growth factor receptor (VEGFR) 2(+) mononuclear cells and collateral vessel remodeling in a mouse model of hind-limb ischemia. These researchers observed that treatment of Sv129 mice with continuous infusion of 200-μg/kg rhIL-11 per day led to in-vivo mobilization of CD34(+)/VEGFR2(+) cells that peaked at 72 hours. Sv129 mice pre-treated with rhIL-11 for 72 hours before femoral artery ligation showed a 3-fold increase in plantar vessel perfusion, leading to faster blood flow recovery; and a 20-fold increase in circulating CD34(+)/VEGFR2(+) cells after 8 days of rhIL-11 treatment. Histologically, experimental mice had a 3-fold increase in collateral vessel luminal diameter after 21 days of rhIL-11 treatment and a 4.4-fold influx of peri-vascular CD34(+)/VEGFR2(+) cells after 8 days of therapy. Functionally, rhIL-11-treated mice showed better hind-limb appearance and use scores when compared with syngeneic mice treated with PBS under the same experimental conditions. The authors concluded that these novel findings showed that rhIL-11 promoted in-vivo mobilization of CD34(+)/VEGFR2(+) mononuclear cells, enhanced collateral vessel growth, and increased recovery of perfusion after femoral artery ligation. They stated that rhIL-11 has a promising role for development as an adjunctive treatment of patients with peripheral vascular disease.

CPT Codes / HCPCS Codes / ICD-10 Codes
Information in the [brackets] below has been added for clarification purposes.   Codes requiring a 7th character are represented by "+":
ICD-10 codes will become effective as of October 1, 2015:
Other CPT codes related to the CPB:
96372 Therapeutic, prophylactic, or diagnostic injection (specify substance or drug); subcutaneous or intramuscular
HCPCS codes covered if selection criteria are met :
J2355 Injection, oprelvekin, 5 mg
ICD-10 codes covered if selection criteria are met:
C00.0 - C91.92, C93.00 - D09.9 Malignant neoplasms [excluding non- myeloid malignancies]


The above policy is based on the following references:
    1. Wyeth Pharmaceuticals, Inc. Neumega (oprelvekin). Prescribing Information. LAB-0455-1.0. Philadelphia, PA: Wyeth; revised January 2011.
    2. No authors listed. Recombinant interleukin-11 for chemotherapy-induced thrombocytopenia. Med Lett Drugs Ther. 1998;40(1032):77-78.
    3. Isaacs C, Robert NJ, Bailey FA, et al. Randomized placebo-controlled study of recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in patients with breast cancer receiving dose-intensive cyclophosphamide and doxorubicin. J Clin Oncol. 1997;15(11):3368-3377.
    4. Wilde MI, Faulds D. Oprelvekin: A review of its pharmacology and therapeutic potential in chemotherapy-induced thrombocytopenia. BioDrugs. 1998;10(2):159-171. 
    5. Ragni MV, Jankowitz RC, Jaworski K, et al. Phase II prospective open-label trial of recombinant interleukin-11 in women with mild von Willebrand disease and refractory menorrhagia. Thromb Haemost. 2011;106(4):641-645
    6. Aitsebaomo J, Srivastava S, Zhang H, et al. Recombinant human interleukin-11 treatment enhances collateral vessel growth after femoral artery ligation. Arterioscler Thromb Vasc Biol. 2011;31(2):306-312
    7. Ragni MV, Novelli EM, Murshed A, et al. Phase II prospective open-label trial of recombinant interleukin-11 in desmopressin-unresponsive von Willebrand disease and mild or moderate haemophilia A. Thromb Haemost. 2013;109(2):248-254
    8. Suliman MI, Qayum I, Saeed F. Randomized clinical trial of human interleukin-11 in Dengue fever-associated thrombocytopenia. J Coll Physicians Surg Pak. 2014;24(3):164-168
    9. Rick ME. Treatment of von Willebrand disease. UpToDate Inc., Waltham, MA. Last reviewed August 2015
    10. Hoots WK, Shapiro AD. Treatment of hemophilia. UpToDate Inc., Waltham, MA. Last reviewed August 2015
    11. Rothman AL, Srikiatkhachorn A, Kalayanarooj S. Prevention and treatment of dengue virus infection. UpToDate Inc., Waltham, MA. Last reviewed August 2015.


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