The safety and efficacy of Darzalex were demonstrated in two open-label studies. In one study of 106 participants receiving Darzalex, 29 percent of patients experienced a complete or partial reduction in their tumor burden, which lasted for an average of 7.4 months. In the second study of 42 participants receiving Darzalex, 36 percent had a complete or partial reduction in their tumor burden. The most common side effects of Darzalex were infusion-related reactions, fatigue, nausea, back pain, fever and cough. Darzalex may also result in low counts of infection-fighting white blood cells (lymphopenia, neutropenia, and leukopenia) or red blood cells (anemia) and low levels of blood platelets (thrombocytopenia).

Darzalex in combination with lenalidomide and low-dose dexamethasone for treatment of patients with multiple myeloma who had received at least one prior therapy was studied in a phase 3, open-label, randomized, active controlled trial versus lenalidomide and low-dose dexamethasone alone. A total of 569 patients were randomized: 286 to the darzalex, lenalidomide and low-dose dexamethasone arm and 283 to the lenalidomide and low-dose dexamethasone arm. Efficacy was evaluated by progression free survival (PFS) based on International Myeloma Working Group (IMWG) criteria. The median PFS was not reached in the darzalex, lenalidomide and low-dose dexamethasone arm and was 18.4 months in the lenalidomide and low-dose dexamethasone arm (hazard ratio [HR]=0.37; 95% CI: 0.27, 0.52; p<0.0001), representing a 63% reduction in the risk of disease progression or death in patients treated with darzalex, lenalidomide and low-dose dexamethasoneversus lenalidomide and low-dose dexamethasone.

Darzalex in combination with bortezomib and dexamethasone for treatment of patients with multiple myeloma who had received at least one prior therapy was studied in a phase 3, open-label, randomized, active-controlled trial versus bortezomib and dexamethasone alone. A total of 498 patients were randomized: 251 to the Darzalex, bortezomib and dexamethasone arm and 247 to the bortezomib and dexamethasone arm. Efficacy was evaluated by progression free survival (PFS) based on International Myeloma Working Group (IMWG) criteria. The median PFS was not reached in the Darzalex, bortezomib and dexamethasone arm and was 7.2 months in the bortezomib and dexamethasone arm (HR [95% CI]: 0.39 [0.28, 0.53]; p-value < 0.0001), representing a 61% reduction in the risk of disease progression or death for patients treated with Darzalex, bortezomib and dexamethasone versus bortezomib and dexamethasone.

Darzalex in combination with bortezomib, melphalan, and prednisone (VMP) for the treatment of patients ineligible for autologous stem cell transplant was based on a phase 3 trial comparing Darzalex 16 mg/kg in combination with VMP (D-VMP) to treatment with VMP in patients with newly diagnosed multiple myeloma. A total of 706 patients were randomized, 350 to the D-VMP group and 356 to the VMP group. Efficacy was evaluated by progression free survival; median progression free survival has still not yet been reached in the D-VMP arm while the VMP group had a PFS of 18.1 months (hazard ratio [HR]=0.5; 95% CI: 0.38, 0.65; p<0.0001), resulting in a 50% reduction in the risk of disease progression or death.

Darzalex in combination with lenalidomide and dexamethasone in patients ineligible for autologous stem cell transplant was based on a phase 3 trial comparing Darzalex 16mg/kg in combination with lenalidomide and low-dose dexamethasone (DRd) to treatment with lenalidomide and low-dose dexamethasone (Rd) in patients with newly diagnosed multiple myeloma. A total of 737 patients were randomized: 368 to the DRd arm and 369 to the Rd arm. Efficacy was evaluated by progression free survival (PFS) based on International Myeloma Working Group (IMWG) criteria. DRd arm as compared to the Rd arm; the median PFS had not been reached in the DRd arm and was 31.9 months in the Rd arm (hazard ratio [HR]=0.56; 95% CI: 0.43, 0.73; p<0.0001), representing 44% reduction in the risk of disease progression or death in patients treated with DRd. In responders, the median time to response was 1.05 months (range: 0.2 to 12.1 months) in the DRd group and 1.05 months (range: 0.3 to 15.3 months) in the Rd group. The median duration of response had not been reached in the DRd group and was 34.7 months (95% CI: 30.8, not estimable) in the Rd group.

Darzalex in combination with bortezomib, thalidomide and dexamethasone (VTd) for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant was based on an open-label, phase 3 trial. The study included 1085 patients with newly diagnosed, previously untreated, symptomatic multiple myeloma who were eligible for high-dose chemotherapy and ASCT. To be eligible for enrollment, patients had to have an ECOG performance status of 0 to 2. The primary endpoint of part 1 of the trial was proportion of patients who achieved stringent complete response (sCR). The second part of CASSIOPEIA is ongoing, and includes patients who achieved a partial response or better in part 1 of the trial who will undergo a second randomization to receive either a maintenance dose of Darzalex at 16 mg/kg every 8 weeks for up to 2 years, or observation. The primary endpoint of this phase of the study is progression-free survival (PFS). At a median follow-up of 18.8 months, the overall response rate (ORR) post-consolidation therapy was 93% with D-VTd and 90% with VTd; the ≥ complete response (≥CR) rates were 39% and 26%, respectively. Additionally, the CR rates were 10% and 6%, and the very good partial response (VGPR) rates were 45% and 52%, respectively. The partial response rates were 9% and 12% for the D-VTd and VTd-alone arms, respectively. The median PFS had not yet been reached in either arm at a median follow-up of 18.8 months, and the Darzalex regimen showed a 53% reduction in the risk of disease progression or death. The 18-month PFS rate was 93% with the Darzalex regimen and 85% with VTd alone, and the PFS benefit was observed across all patient subgroups.

Darzalex in combination with carfilzomib and dexamethasone was FDA approved for the treatment of patients with relapsed or refractory multiple myeloma who had received 1 to 3 lines of prior therapy. This approval was based on 2 trials: CANDOR (NCT03158688) and EQUULEUS (NCT01998971)

CANDOR (NCT03158688) was a randomized, open-label, multicenter trial which evaluated the combination of DARZALEX with twice-weekly carfilzomib and dexamethasone (DKd) versus twice-weekly carfilzomib and dexamethasone (Kd) in patients with relapsed or refractory multiple myeloma who had received at least 1 to 3 prior lines of therapy. Patients who had the following were excluded from the trial: known moderate or severe persistent asthma within the past 2 years, known chronic obstructive pulmonary disease (COPD) with a FEV1 75 years on a reduced dexamethasone dose of 20 mg, the entire 20 mg dose was given as a DARZALEX pre-infusion medication on days when DARZALEX was administered. Dosing of dexamethasone was otherwise split across days when carfilzomib was administered in both study arms. Treatment was continued in both arms until disease progression or unacceptable toxicity. A total of 466 patients were randomized; 312 to the DKd arm and 154 to the Kd arm. Patients had received a median of 2 prior lines of therapy and 58% of patients had received prior autologous stem cell transplantation (ASCT). The majority of patients (92%) received a prior PI and of those 34% were refractory to PI including regimen. Fourty-two percent (42%) of patients had received prior lenalidomide and of those, 33% were refractory to a lenalidomide containing regimen. CANDOR demonstrated an improvement in PFS in the DKd arm as compared to the Kd arm; the median PFS had not been reached in the DKd arm and was 15.8 months in the Kd arm (hazard ratio [HR]=0.63; 95% CI: 0.46, 0.85; p=0.0014), representing 37% reduction in the risk of disease progression or death for patients treated with DKd versus Kd. The median time to response was 1 month (range: 1 to 14 months) in the DKd group and 1 month (range: 1 to 10 months) in the Kd group. The median duration of response had not been reached in the DKd group and was 16.6 months (95% CI: 13.9, not estimable) in the Kd group.

EQUULEUS (NCT01998971) was an open-label, multi-cohort trial which evaluated the combination of DARZALEX with one-weekly carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who had received at least 1 to 3 prior lines of therapy. Patients who had the following were excluded from the trial: known moderate or severe persistent asthma within the past 2 years, known chronic obstructive pulmonary disease (COPD) with a FEV1 <50% of predicted normal, or active congestive heart failure (defined as New York Heart Association Class III-IV). Ten patients were administered DARZALEX at a dose of 16 mg/kg intravenously on Cycle 1, Day 1 and the remaining patients were administered DARZALEX at a dose of 8 mg/kg intravenously on Cycle 1, Days 1 and 2. Thereafter, DARZALEX was administered intravenously at a dose of 16 mg/kg on Days 8, 15 and 22 of Cycle 1; Days 1, 8, 15 and 22 of Cycle 2; Days 1 and 15 of Cycles 3 to 6; and then Day 1 for the remaining cycles of each 28 day cycle. Carfilzomib was administered intravenously once weekly at a dose of 20 mg/m2 on Cycle 1 Day 1 and escalated to dose of 70 mg/m2 on Cycle 1 Days 8 and 15, and Days 1, 8, and 15 of each subsequent 28-day cycle. In Cycles 1 and 2, dexamethasone 20 mg was administered orally or intravenously on Days 1, 2, 8, 9, 15, 16, 22 and 23; in cycles 3 to 6, dexamethasone 20 mg was administered orally or intravenously on Days 1, 2, 15 and 16 and at a dose of 40 mg on Day 8 and 22; and in cycles 7 and thereafter, dexamethasone 20 mg was administered orally or intravenously on Days 1 and 2 and at a dose of 40 mg on Days 8, 15, and 22. For patients >75 years of age, dexamethasone 20 mg was administered orally or intravenously weekly after the first week. Treatment continued until disease progression or unacceptable toxicity. The EQUULEUS trial enrolled 85 patients. Patients in the study had received a median of 2 prior lines of therapy. Seventy-three percent (73%) of patients had received prior ASCT. All patients received prior bortezomib, and 95% of patients received prior lenalidomide. Fifty-nine percent (59%) of patients were refractory to lenalidomide and 29% of patients were refractory to both a PI an IMiD. The median time to response was 0.95 months (range: 0.9, 14.3). The median duration of response was 28 months (95% CI: 20.5, not estimable).

On May 1, 2020, the U.S. Food and Drug Administration (FDA) approved Darzalex Faspro™ (daratumumab and hyaluronidase-fihj), a new subcutaneous formulation of daratumumab. Darzalex Faspro™ is approved in four regimens across five indications in multiple myeloma patients, including newly diagnosed, transplant-ineligible patients as well as relapsed or refractory patients. As a fixed-dose formulation, it can be administered over approximately three to five minutes, less time than Darzalex^®, which is given intravenously over hours. Darzalex Faspro™ is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) [Halozyme's ENHANZE^® drug delivery technology].

Darzalex Faspro™ is approved in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant, in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy, in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy, as monotherapy, in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent. The approval is based on data from the Phase 3 COLUMBA (NCT03277105) and Phase 2 PLEIADES (NCT03412565) studies.

In the COLUMBA study, the ORR was non-inferior for patients taking Darzalex Faspro™ as monotherapy compared to those taking intravenous Darzalex^® as monotherapy (41% vs. 37%, respectively). In addition, there were fewer systemic adverse reactions with Darzalex Faspro™ versus intravenous Darzalex^® (13% vs. 34%, respectively). The randomized, open-label, multicenter Phase 3 COLUMBA study included 522 patients (median age of 67 years) with multiple myeloma who had received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or whose disease was refractory to both a PI and an IMiD. In the arm that received Darzalex Faspro™ (n=263), patients received a fixed dose of Darzalex Faspro™ 1,800 milligrams (mg), co-formulated with recombinant human hyaluronidase PH20 (rHuPH20) 2,000 Units per milliliter (U/mL), subcutaneously weekly for Cycles 1 – 2, every two weeks for Cycles 3 – 6 and every four weeks for Cycle 7 and thereafter. In the intravenous Darzalex^® arm (n=259), patients received Darzalex^® for intravenous infusion 16 milligrams per kilogram (mg/kg) weekly for Cycles 1 – 2, every two weeks for Cycles 3 – 6 and every four weeks for Cycle 7 and thereafter. Each cycle was 28 days. In the arm that received Darzalex Faspro™, it was given in a fixed volume of 15 mL over three to five minutes; the median injection time was five minutes. In the arm that received the intravenous administration, the median durations of the first, second and subsequent intravenous Darzalex^® infusions were 7.0, 4.3 and 3.4 hours, respectively. Patients in both arms continued treatment until disease progression or unacceptable toxicity.

Additionally, in the Phase 2 PLEIADES study evaluating the efficacy and safety of Darzalex Faspro™ in combination therapies, objective responses were demonstrated in combination with bortezomib, melphalan and prednisone (D-VMP) in newly diagnosed transplant ineligible patients. In addition, objective responses were demonstrated in combination with lenalidomide and dexamethasone (D-Rd) in relapsed or refractory patients who received one prior line of therapy. The non-randomized, open-label, parallel assignment Phase 2 PLEIADES study included more than 240 adults with multiple myeloma, including 67 patients with newly diagnosed multiple myeloma who were treated with 1,800 mg of Darzalex Faspro™ in combination with bortezomib, melphalan, and prednisone (D-VMP) and 65 patients with relapsed or refractory disease who were treated with 1,800 mg of Darzalex Faspro™ plus lenalidomide and dexamethasone (D-Rd). The primary endpoint for the D-VMP and D-Rd cohorts was overall response rate.

As per the FDA labeled package insert, the most common adverse reaction (≥20%) with Darzalex Faspro™ monotherapy is: upper respiratory tracts infection. The most common adverse reactions (≥20%) with D-VMP are upper respiratory tract infection, constipation, nausea, fatigue, pyrexia, peripheral sensory neuropathy, diarrhea, cough, insomnia, vomiting, and back pain. The most common adverse reactions (≥20%) with D-Rd are fatigue, diarrhea, upper respiratory tract infection, muscle spasms, constipation, pyrexia, pneumonia and dyspnea. The most common hematology laboratory abnormalities (≥40%) with Darzalex Faspro™ are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.

Policy:
(NOTE: For Medicare Advantage, please refer to the Medicare Coverage Section below for coverage guidance)

The requirements of the Horizon BCBSNJ Daratumumab (Darzalex) Program may require a precertification/prior authorization via MagellanRx Management. These requirements are member-specific: please verify member eligibility and requirements through the Horizon Provider Portal (www.horizonblue.com/provider). Ordering clinicians should request pre-certification from MagellanRx Management at ih.magellanrx.com or call 1-800-424-4508 (when applicable).

I. Darzalex^® (daratumumab)

a. Darzalex^® (daratumumab) is medically necessary for the treatment of adult members (>= 18 years old) with multiple myeloma in members that meet ALL of the following criteria:

i. Member has received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent OR who are double-refractory to a PI and an immunomodulatory agent AND will be used monotherapy; OR
ii. Member has received at least one prior therapy AND will be used in combination with lenalidomide and dexamethasone OR bortezomib and dexamethasone; OR
iii. Member has received at least two prior lines of therapy including lenalidomide and a proteasome inhibitor (PI) (e.g., bortezomib) AND will be used in combination with pomalidomide and dexamethasone; OR
iv. Member will receive in combination with bortezominb, melphalan, and prednisone for the treatment of newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; OR
v. Member will receive in combination with lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; OR
vi. Member will receive in combination with bortezomib, thalidomide and dexamethasone for the treatment of patients with newly diagnosed multiple myeloma who are eligible for autologous stem cell transplant; OR
vii. Member will receive in combination with carfilzomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy; AND
viii. The prescriber is a specialist in the area of the patient's diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient's diagnosis.

b. When Darzalex^® (daratumumab) is medically necessary, therapy will be approved for 6 months based on FDA recommendations:
i. Administered via intravenous infusion at a dose of 16 mg/kg actual body weight (unless noted otherwise below)
ii. The dosing frequency will be based on Table 1 if used as monotherapy therapy or in combination with lenalidomide or pomalidomide and low-dose dexamethasone
iii. The dosing frequency will be based on Table 2 if used in combination with bortezomib and dexamethasone for patients with relapsed/refractory multiple myeloma
iv. The dosing frequency will be based on Table 3 if used in combination with bortezomib, melphalan, and prednisone for patients with newly diagnosed multiple myeloma ineligible for autologous stem cell transplant
v. The dosing frequency will be based on Table 4 if used in combination with bortezomib, thalidomide, and dexamethasone for patients newly diagnosed with multiple myeloma eligible for autologous stem cell transplant.
vi. The dosing frequency will be based on Table 5 if used in combination with carfilzomib and dexamethasone for patients with relapsed/refractory multiple myeloma
vii. Member will receive pre-infusion and post-infusion medications to decrease the risk of infusion reactions
viii. Interrupt Darzalex infusion for infusion reactions of any severity. Permanently discontinue the infusion in case of life threatening infusion reactions.
Table 1

Schedule	Weeks
Weekly (total of 8 doses)	Weeks 1 to 8
Every two weeks (total of 8 doses)	Weeks 9 to 24
Every four weeks	Weeks 25 onwards until disease progression

Table 2

Schedule	Weeks
Weekly(total of 9 doses)	Weeks 1 to 9
Every three weeks (total of 5 doses)	Weeks 10 to 24
Every four weeks	Week 25 onwards until disease progression


Table 3

Schedule	Weeks
Weekly (total of 6 doses)	Weeks 1 to 6
Every three weeks (total of 16 doses)	Weeks 7 to 54
Every four weeks	Week 55 onwards until disease progression

Table 4

Schedule	Weeks
Induction
Weekly (total of 8 doses)	Weeks 1 to 8
Every two weeks (total of 4 doses)	Weeks 9 to 16
Stop for high dose chemotherapy and ASCT
Consolidation
Every two weeks (total of 4 doses)	Weeks 1 to 8


Table 5

Schedule	Weeks	Darzalex Dose
Days 1 and 2 (total 2 doses)	Week 1	8 mg/kg
Weekly (total of 7 doses)	Weeks 2 to 8	16 mg/kg
Every 2 weeks (total of 8 doses)	Weeks 9 to 24	16 mg/kg
Every four weeks	Week 25 onwards until disease progression	16 mg/kg


(*) To facilitate administration, the first prescribed 16 mg/kg dose at Week 1 could be split over 2 consecutive days. Table below describes the 2 options for initial infusions




Week 1 Infusion

Option1 (Single dose infusion)

Week 1 Day 1 (16mg/kg)

Option 2 (Split dose infusion)

Week 1 Day 1 (8mg/kg)

Week 1 Day 2 (8mg/kg)


c. Medical necessity for continued therapy with Darzalex^® (daratumumab) will be approved every 12 months if the member meets the following criteria:
• Member continues to meet initial review criteria; AND
• Tumor response with stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug (e.g.: severe infusion reactions, neutropenia, thrombocytopenia, etc.)
d. Darzalex^® (daratumumab) is considered medically necessary for off-label indications that have in effect a rating of ‘Category 1’ or ‘Category 2A’ in the current recommendations in the National Comprehensive Cancer Network (NCCN) compendium. Refer to National Comprehensive Cancer Network: Drugs and Biologics Compendium - daratumumab. Available at: https://www.nccn.org/professionals/drug_compendium/content/

e. Darzalex^® (daratumumab) for the treatment of other conditions/diseases is considered investigational.

a. Darzalex Faspro™ (daratumumab and hyaluronidase-fihj) is medically necessary for the treatment of adult members (>= 18 years old) with multiple myeloma in members that meet ALL of the following criteria:

i. Member has received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent OR who are double-refractory to a PI and an immunomodulatory agent AND will be used monotherapy; OR
ii. Member has received at least one prior therapy AND will be used in combination with lenalidomide and dexamethasone OR bortezomib and dexamethasone; OR
iii. Member will receive in combination with bortezominb, melphalan, and prednisone for the treatment of newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; OR
iv. Member will receive in combination with lenalidomide and dexamethasone for the treatment of newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant; AND
v. The prescriber is a specialist in the area of the patient's diagnosis (e.g. oncologist) or has consulted with a specialist in the area of the patient's diagnosis.

b. When Darzalex Faspro™ (daratumumab and hyaluronidase-fihj) is medically necessary, therapy will be approved for 6 months based on FDA recommendations:
i. Administered subcutaneously only
ii. The recommended dose is 1,800 mg/30,000 units (1,800mg daratumumab and 30,000 units hyaluronidase) administered subcutaneously over approximately 3-5 minutes
iii. The dosing frequency will be based on Table 1 if used as monotherapy therapy or in combination with lenalidomide and dexamethasone
iv. The dosing frequency will be based on Table 2 if used in combination with bortezomib, melphalan, and prednisone
v. The dosing frequency will be based on Table 3 if used in combination with bortezomib, and dexamethasone
vi. Member will receive pre-infusion and post-infusion medications to decrease the risk of infusion reactions

Table 1

Schedule	Weeks
Weekly (total of 8 doses)	Weeks 1 to 8
Every two weeks (total of 8 doses)	Weeks 9 to 24
Every four weeks	Weeks 25 onwards until disease progression

Table 2

Schedule	Weeks
Weekly (total of 6 doses)	Weeks 1 to 6
Every three weeks (total of 16 doses)	Weeks 7 to 54
Every four weeks	Week 55 onwards until disease progression


Table 3

Schedule	Weeks
Weekly(total of 9 doses)	Weeks 1 to 9
Every three weeks (total of 5 doses)	Weeks 10 to 24
Every four weeks	Week 25 onwards until disease progression

[INFORMATIONAL NOTE: As per the FDA labeled package insert dosing section, no dose reductions of Darzalex Faspro are recommended. Consider withholding Darzalex Faspro to allow recovery of blood cell counts in the event of myelosuppression.]
c. Medical necessity for continued therapy with Darzalex Faspro™ (daratumumab and hyaluronidase-fihj) will be approved every 12 months if the member meets the following criteria:
• Member continues to meet initial review criteria; AND
• Tumor response with stabilization of disease or decrease in size of tumor or tumor spread; AND
• Absence of unacceptable toxicity from the drug (e.g.: hypersensitivity and other administration reactions, neutropenia, thrombocytopenia, etc.)
d. Darzalex Faspro™ (daratumumab and hyaluronidase-fihj) for the treatment of other conditions/diseases is considered investigational.

There is no National Coverage Determination (NCD) or Local Coverage Determination (LCD) for jurisdiction JL specifically for these drugs. Therefore, Medicare Advantage Products will follow the Horizon BCBSNJ medical policy.

Darzalex Faspro™ is administered subcutaneously. Per Local Coverage Article A53127 Self-Administered Drug Exclusion List, drugs administered subcutaneously are considered to be usually self-administered. Medicare covers drugs that are furnished “incident to” a physician’s service provided that the drugs are medically reasonable and necessary, approved by the Food and Drug Administration (FDA) and are not usually administered by the patients who take them. Therefore, Medicare Advantage Products will cover Darzalex Faspro™ when the Horizon BCBSNJ Medical Policy criteria is met AND the drug is furnished and administered by a licensed medical provider as part of a physician service.

For additional information, refer to Novitas Solutions, Inc., Local Coverage Article: Self-Administered Drug Exclusion List: (A53127). Available to be accessed at Novitas Solutions, Inc., Medical Policy Search page: https://www.novitas-solutions.com/webcenter/portal/MedicareJL/pagebyid?contentId=00024370.

Medicaid Coverage

For Horizon NJ Health members, please follow this link for the corresponding HNJH drug policy https://services3.horizon-bcbsnj.com/ddn/NJhealthWeb.nsf

________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Daratumumab (Darzalex)
Darzalex (Daratumumab)
Darzalex Faspro (daratumumab and hyaluronidase-fihj)
Daratumumab and hyaluronidase-fihj (Darzalex Faspro)

References:

1. Darzalex^® [package insert]. Janssen Biotech. Horsham, PA. August 2020.

2. Darzalex^® [Dossier]. Janssen Biotech. Horsham, PA. November 2015.

3. FDA News Release: FDA approves Darzalex for patients with previously treated multiple myeloma. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm472875.htm

4. Lokhorst HM, Plesner T, Laubach JP, et al. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. N Engl J Med 2015; 373:1207-1219. September 24, 2015. DOI: 10.1056/NEJMoa1506348.

5. Phipps C, Chen Y, Gopalakrishnan S, Tan D. Daratumumab and its potential in the treatment of multiple myeloma: overview of the preclinical and clinical development. Ther Adv Hematol. 2015 Jun;6(3):120-7. doi: 10.1177/2040620715572295.

6. ClinicalTrials.gov accessed 17 January 2020 at https://clinicaltrials.gov/ct2/results?term= Daratumumab=Search

7. Dimopoulos MA, Oriol A, Nahi H, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Eng J Med 2016; 375:1319-1331. October 6, 2016. DOI: 10.1056/NEJMoa1607751

8. Palumbo A, Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med 2016; 375(8):754-766. August 25, 2016. DOI: 10.1056/NEJMoa1606038.

9. Referenced with permission from the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for daratumumab. National Comprehensive Cancer Network, 2020. The NCCN Compendium® is a derivative work of the NCCN Guidelines®. Accessed January 2020.

10. Chari, A., Suvannasankha, A., Fay, J. W., Arnulf, B., Kaufman, J. L., Ifthikharuddin, J. J., Weiss, B. M., Krishnan, A., Lentzsch, S., Comenzo, R., Wang, J., Nottage, K., Chiu, C., Khokhar, N. Z., Ahmadi, T., & Lonial, S. (2017). Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood, (), blood-2017-05-785246.

11. ClinicalTrials.gov. Study Comparing Daratumumab, Lenalidomide, and Dexamethasone with Lenalidomide and Dexamethasone in Participants with Previously Untreated Multiple Myeloma. Accessed August 2019. Accessed at: https://clinicaltrials.gov/ct2/show/NCT02252172?term=NCT02252172&rank=1.

12. New Indication For Darzalex Approved by FDA. Multiple Myeloma, New Products, The Latest. Modern Medicine Network. Available at: https://www.drugtopics.com/multiple-myeloma/new-indication-darzalex-approved-fda

13. FDA Grants Indication for Daratumumab Plus Combo in Newly Diagnosed Multiple Myeloma With Transplant. AJMC. Accessed October 2019. Available at: https://www.ajmc.com/newsroom/fda-grants-indication-for-daratumumab-plus-combo-in-newly-diagnosed-multiple-myeloma-with-transplant

14. Darzalex Faspro™ (daratumumab and hyaluronidase-fihj) [package insert]. Janssen Biotech. Horsham, PA. April 2020.

15. U.S Food and Drug Administration Approves Darzalex Faspro™ (daratumumab and hyaluronidase-fihj), a New Subcutaneous Formulation of Daratumumab in the Treatment of Patients with Multiple Myeloma. BioSpace. Source: The Janssen Pharmaceutical Companies of Johnson & Johnson. May 1, 2020. Available at: https://www.biospace.com/article/releases/u-s-food-and-drug-administration-approves-darzalex-faspro-daratumumab-and-hyaluronidase-fihj-a-new-subcutaneous-formulation-of-daratumumab-in-the-treatment-of-patients-with-multiple-myeloma/


Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*