Prior Auth Protocol

FDA Approved Indications:

Treatment of patients with transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities
Multiple myeloma, in combination with dexamethasone
Treatment of patients with mantle cell lymphoma (MCL) whose disease has relapsed or progressed after two prior therapies, one of which included bortezomib (Velcade^R)

Health Net Approved Indications and Usage Guidelines:

Transfusion-dependent anemia

Diagnosis of transfusion-dependent anemia due to low- or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion 5q abnormality with or without additional cytogenetic abnormalities

Multiple Myeloma

Diagnosis of Multiple Myeloma (MM)

AND

Must be used in combination with dexamethasone unless contraindicated

Mantle Cell Lymphoma

Diagnosis of mantle cell lymphoma

AND

Failure or clinically significant adverse effects to at least two prior chemotherapies (including CHOP [Cytoxan^R, Adriamycin^R, vincristine, and prednisone] and hyperCVAD [Cytoxan, vincristine, Adriamycin, and dexamethasone]) including Velcade unless contraindicated

Amyloidosis

Diagnosis of systemic light chain amyloidosis

AND

Must be used in combination with dexamethasone unless contraindicated

Coverage is Not Authorized For:

Non-FDA approved indications, which are not listed in the Health Net Approved Indications and Usage Guidelines section, unless there is sufficient documentation of efficacy and safety in the published literature.

General Information:

Anemia is defined as hemoglobin level less than 10 g/dl.
Transfusion dependence was defined in two different studies as either greater than 2 units or greater than 4 units of RBCs within 8 weeks prior to enrollment into the studies.
According to National Comprehensive Cancer Network (NCCN) guideline, the following are 2A recommendations: a) MDS with no deletion of 5q with a low probability of response to immunosuppressive therapy, b) systemic light chain amyloidosis, and c) second line therapy for Non-Hodgkins Lymphoma (AIDS Related B-Cell Lymphoma, Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Gastric and Nongastric MALT Lymphoma, Mantle Cell Lymphoma, Primary Cutaneous B-Cell Lymphoma, and Splenic Marginal Zone Lymphoma).
According to NCCN guideline, category 1 recommendation for the treatment of MM is listed as follows: a) maintenance therapy when in remission: Revlimid, Thalomid^R, and b) salvage therapy: Velcade^R, Velcade^R/liposomal doxorubicin, Revlimid/dexamethasone. Salvage therapy is used in patients who have relapse following allogeneic or autologous stem cell transplant or in patients with primary progressive disease following allogeneic or autologous stem cell transplant. Salvage therapy can also be used in patients who are ineligible for stem cell transplant with progressive or relapsing disease after initial induction therapy.
According to NCCN guideline, current drug therapies for MCL include: a) induction therapy (including CHOP [Cytoxan, Adriamycin, vincristine, and prednisone] and hyperCVAD [Cytoxan, vincristine, Adriamycin, and dexamethasone] - given in frequent smaller doses, and b) second-line therapy (including Velcade+Rituxan^R and Revlimid+Rituxan).
In the pivotal trial, patients with MCL were required to have received prior treatment with an anthracycline or mitoxantrone, cyclophosphamide, Rituxan^R, and Velcade^R, alone or in combination. Among these agents, Velcade^R is the only FDA approved medication indicated for the treatment of MCL.
Inclusion criteria for studies with Revlimid allowed for previous use of Thalomid^R in patients with refractory/relapsing MM. Eight percent of patients previously treated with Thalomid^R demonstrated a complete response with 53.3% showing an overall response to Revlimid + Dexamethasone and 45.2% demonstrating a partial response.
The FDA notified the public of an increased risk of second primary malignancies in patients with newly-diagnosed MM who received Revlimid. Clinical trials conducted after Revlimid was approved showed that newly-diagnosed patients treated with Revlimid had an increased risk of developing acute myelogenous leukemia, myelodysplastic syndromes, and Hodgkin lymphoma.
Revlimid is only available under a restricted distribution program called "RevAssist" due to the black box warning for fetal risk, hematologic toxicity, and deep vein thrombosis/pulmonary embolism. Patient and physician enrollment in the manufacturer's REMS program is required.

Therapeutic Alternatives:

Drug	Dosing Regimen	Dose Limit/ Maximum Dose
melphalan/prednisone (MP)	Multiple Myeloma (Conventional primary therapy) Melphalan: 8 mg/m²/day PO days 1-4 Prednisone: 60 mg/m²/day PO days 1-4 Repeat cycle every 28 days	As recommended in dosing regimen
vincristine/doxorubicin/dexamethasone (VAD)	Multiple Myeloma (Conventional primary therapy) Vincristine: 0.4 mg/day IV continuous infusion days 1-4 Doxorubicin: 9 mg/ m²/day IV continuous infusion days 1-4 Dexamethasone: 40 mg PO days 1-4, 9-12, 17-20 Repeat cycle every 28-35 days	As recommended in dosing regimen
dexamethasone (pulse dose as single agent)	Multiple Myeloma (Conventional primary therapy) Dexamethasone: 40 mg PO days 1-4, 9-12, 17-20	As recommended in dosing regimen
Thalomid^R (thalidomide)*/ dexamethasone	Multiple Myeloma (Conventional primary therapy) Thalidomide: 200 mg/day PO daily Dexamethasone: 40 mg/day days 1-4,9-12,17-20 for odd cycles and days 1-4 for even cycles Repeat cycle every 28 days	As recommended in dosing regimen
Velcade^R(bortezomib)*	Mantle Cell Lymphoma 1.3 mg/m²/dose SC or IV BIW for 2 weeks (Days 1, 4, 8, and 11) followed by a 10-day rest period (Days 12-21). For extended therapy of more than 8 cycles, Velcade may be administered on the standard schedule or on a maintenance schedule of once weekly for 4 weeks (Days 1, 8, 15, and 22) followed by a 13-day rest period (Days 23 to 35). At least 72 hours should elapse between consecutive doses of Velcade	1.3 mg/m²/dose
Pomalyst^R(pomalidomide)	Multiple Myeloma 4 mg PO QD on days 1-21 of repeated 28-day cycles until disease progression. Pomalyst may be given in combination with dexamethasone Avoid Pomalyst in patients with a serum creatinine greater than 3.0 mg/dL	This field intentionally left blank.

* Requires Prior Authorization

Recommended Dosing Regimen and Authorization Limit:

Drug	Dosing Regimen	Authorization Limit
Revlimid	Myelodysplastic Syndrome 10 mg PO QD Dosing is modified based upon clinical and laboratory findings Multiple Myeloma (newly diagnosed patients) 25 mg PO QD days 1-21 of repeated 28 day cycles with dexamethasone 40 mg PO QD on days 1, 8, 15, 22 of each 28 day cycle. Dosing is modified based upon clinical and laboratory findings Multiple Myeloma (previously treated patients) 25 mg PO QD days 1-21 of repeated 28 days cycles with dexamethasone 40 mg QD days 1-4, 9-12 and 17-20 of each 28 day cycle for the first 4 cycles then 40 mg QD for days 1-4 every 28 days. Dosing is modified based upon clinical and laboratory findings Mantle Cell Lymphoma 25 mg PO QD on Days 1-21 of repeated 28-day cycles. Dosing is modified based upon clinical and laboratory findings Amyloidosis 25 mg PO QD days 1-21 of repeated 28 days cycles with dexamethasone 40 mg once per week. Dosing of Revlimid can be reduced to 15 mg/day for tolerability and can be combined with dexamethasone and either melphalan or cyclophosphamide	Length of benefit

Product Availability:

Capsule: 2.5 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg

References:

1. Revlimid (Prescribing Information). Summit, NJ: Celgene Corporation; February 2015.

2. List A, Kurtin S, Roe D, et al. Efficacy of Lenalidomide in Myelodysplastic Syndromes. N Engl J Med. 2005; 352 (6): 549-557.

3. National Comprehensive Cancer Network. Myelodysplastic Syndromes Version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/mds.pdf. Accessed July 1, 2014.

4. National Comprehensive Cancer Network. Multiple Melanoma Version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/myeloma.pdf. Accessed July 1, 2014.

5. National Comprehensive Cancer Network. Non-Hodgkins Lymphomas Version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/pdf/nhl.pdf. Accessed July 1, 2014.

6. National Comprehensive Cancer Network. Systemic Light Chain Amyloidosis Version 2.2014. Available at: http://www.nccn.org/professionals/physician_gls/PDF/amyloidosis.pdf. Accessed July 1, 2014.

7. Weber DM, Chen C, et.al. Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 357(21):2133-42, 2007 Nov 22.

8. Lacy MQ, Ertz MA, et.al. Long-term results of response to therapy, time to progression, and survival with lenalidomide plus dexamethasone in newly diagnosed myeloma. Mayo Clinic Proceedings.82 (10):1179-84, 2007 Oct.

9. FDA MedWatch Update. Revlimid: Ongoing Safety Review- Increased Risk of Developing New Malignancies. Available at: http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm250606.htm. Accessed July 1, 2014.