CurrentCentenePolicy CP PHAR.361

Tisagenlecleucel (Kymriah) - Clinical Policy

Policy governing medical necessity and prior authorization criteria for one-time infusion of tisagenlecleucel (Kymriah) for pediatric B-cell precursor ALL and adult large B‑cell and follicular lymphomas for Centene lines of business.

Policy Summary

PayerCentene

PolicyTisagenlecleucel (Kymriah) - Clinical Policy

Policy CodePolicy CP PHAR.361

Change TypeNo material change

Effective DateDec 1, 2017

Next Review Date

Key ActionPrior authorization required with supporting documentation and medical director review; prescribed by or in consultation with an oncologist or hematologist.

SourceLink

POLICY UPDATE CHANGES

No material clinical or coverage changes in this revision.

one doseapproval is for a single (initial) treatment dose only

3 monthsapproval duration (covers dosing and up to 4 tocilizumab doses)

REMS requiredKymriah available only through REMS program

Multiple indicationsdiagnoses discussed in policy appendices

Coverage Criteria

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Initial therapy — B-cell precursor ALL

Covered when ALL of the following are met for initial (one-time) dose:

ALL initial criteria: 1) Prescribed by or in consultation with an oncologist or hematologist; 2) Diagnosis of B-cell precursor acute lymphoblastic leukemia (ALL); 3) Age ≤ 25 years; 4) Documentation of CD19 tumor expression; 5) Recent (within the last 30 days) documentation of one of the following: a) Absolute lymphocyte count (ALC) ≥ 500/µL OR b) disease is refractory, defined as failure to achieve a complete response following induction therapy with ≥2 cycles of standard chemotherapy (primary refractory) or chemorefractory after 1 cycle; 6) Request meets one of the following: a) disease refractory as defined, b) ≥2 relapses, c) relapsed following allogeneic stem cell transplantation and ≥6 months from SCT at time of infusion, d) Philadelphia chromosome positive (Ph+) disease: has received 2 lines of chemotherapy that included 2 tyrosine kinase inhibitors; 7) Member has not previously received CAR T-cell immunotherapy; 8) Kymriah is not prescribed concurrently with other CAR T-cell immunotherapies; 9) Dose does not exceed weight-based limits: if weight <50 kg: up to 5.0 x 10^6 CAR-positive viable T cells/kg; if weight ≥50 kg: up to 2.5 x 10^8 CAR-positive viable T cells;N/A

Approval duration: single initial dose (3 months coverage for dosing logistics) and up to 4 doses of tocilizumab if requested

Initial therapy — Large B-Cell Lymphoma (LBCL)

Covered when ALL of the following are met for initial (one-time) dose:

LBCL initial criteria: 1) Diagnosis of one of the specified LBCL subtypes (examples include DLBCL, transformed follicular lymphoma to DLBCL, primary mediastinal large B‑cell lymphoma [PMBCL], transformed nodal marginal zone lymphoma to DLBCL, monomorphic post‑transplant B‑cell PTLD, high‑grade B‑cell lymphomas with MYC/BCL2 rearrangements, HIV‑related DLBCL, primary effusion lymphoma, HHV8‑positive DLBCL); 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) Recent (within the last 30 days) ALC ≥ 300/µL; 5) Request meets one of the following: a) disease refractory or relapsed after ≥2 lines of systemic therapy that includes rituximab and an anthracycline‑containing regimen; b) disease relapsed >12 months after completion of first‑line therapy with partial response after second‑line therapy (off‑label per NCCN compendium); 6) Member does not have active or primary CNS disease; 7) Member has not previously received CAR T‑cell immunotherapy; 8) Kymriah is not prescribed concurrently with other CAR T‑cell immunotherapies; 9) Dose does not exceed 6.0 x 10^8 CAR‑positive viable T cells (single administration).N/A

Approval duration: single initial dose (3 months coverage) and up to 4 doses of tocilizumab if requested

Initial therapy — Follicular Lymphoma (FL)

Covered when ALL of the following are met for initial (one-time) dose:

FL initial criteria: 1) Diagnosis of follicular lymphoma (FL) grade 1, 2, or 3a; 2) Prescribed by or in consultation with an oncologist or hematologist; 3) Age ≥ 18 years; 4) Disease relapsed or refractory after ≥2 lines of systemic therapy that includes an anti‑CD20 monoclonal antibody (e.g., rituximab or obinutuzumab) plus an alkylating agent (e.g., bendamustine, cyclophosphamide) OR has relapsed following autologous stem cell transplantation; 5) Member has not previously received CAR T‑cell immunotherapy; 6) Member does not have active CNS involvement; 7) Kymriah is not prescribed concurrently with other CAR T‑cell immunotherapies; 8) Dose does not exceed a single administration of 6.0 x 10^8 CAR‑positive viable T cells.N/A

Approval duration: single initial dose (3 months coverage) and up to 4 doses of tocilizumab if requested

Coverage conditions (selected elements present)

Coverage contingent on meeting indication-specific clinical criteria (examples below drawn from appendices and coding implications):

General requirements: Member has a labeled or NCCN‑supported indication appropriate for Kymriah; prior lines of therapy documented when specified by indication; member has not previously received CAR T‑cell therapy; Kymriah will not be given concurrently with other CAR T‑cell therapies; treatment will be provided at a certified facility enrolled in the Kymriah REMS program.

Derived from FDA indication, NCCN alignment, and REMS statements

Leukapheresis eligibility: Manufacturer recommendations for leukapheresis: for ALL, ALC > 500/µL; if ALC < 500/µL during screening then CD3 (T‑cell) count ≥150/µL may be required. The JULIET trial excluded patients with ALC < 300/µL.ALC and CD3 thresholds per manufacturer/trials

Supports required documentation of leukapheresis eligibility

Dosing constraints: Dosing follows weight‑based tiers for ALL (<50 kg: 0.2–5.0 x 10^6 CAR+ viable T cells/kg; ≥50 kg: 0.1–2.5 x 10^8 CAR+ viable T cells) and fixed‑range for LBCL/FL (0.6–6.0 x 10^8 CAR+ viable T cells; maximum single administration 6.0 x 10^8).dose ranges specified

See appendices for full dosing tables and administration requirements

Do not administer Kymriah to patients with active infection or inflammatory disorders; these are contraindications due to risk of severe cytokine release syndrome and other life-threatening reactions. Clinical trials excluded patients with active CNS disease and used explicit screening definitions (see Appendix D) to assess CNS involvement.

While there is no separate explicit "not medically necessary" statement for every scenario, administration of Kymriah outside of its required safety program or in the presence of contraindications would preclude coverage. Specifically, failure to meet REMS enrollment requirements or attempting to treat patients with active infection, inflammatory disorders, or active CNS disease (per trial/exclusion definitions) would render therapy inappropriate.

Coding

Covered HCPCS CodesHCPCSCovered

Q2042

Tisagenlecleucel, up to 600 million CAR-positive viable T cells, including leukapheresis and dose preparation procedures per therapeutic dose

Absolute lymphocyte count (ALC) thresholds

ALC threshold for pediatric B-cell precursor ALL≥ 500/µL (documented within the last 30 days)

ALC threshold for LBCL≥ 300/µL (documented within the last 30 days)

Time window for ALC documentationRecent — within the last 30 days

CAR-positive viable T cell dose limits

Weight < 50 kg dosing tier5.0 x 10^6 CAR+ viable T cells per kg (maximum per kg dosing tier)

Weight ≥ 50 kg fixed-dose tier2.5 x 10^8 CAR+ viable T cells (per dosing tier)

LBCL/FL maximum single administrationMaximum single administration 6.0 x 10^8 CAR+ viable T cells

Leukapheresis eligibility (manufacturer guidance)

Manufacturer leukapheresis ALC recommendationALC > 500/µL for leukapheresis collection (manufacturer recommendation)

If ALC < 500/µL at screeningA CD3 (T-cell) count ≥ 150/µL may be required to be eligible for leukapheresis collection

DocumentationLeukapheresis eligibility data (ALC and CD3 counts) should be included in prior authorization documentation

JULIET trial ALC exclusion

JULIET trial exclusion for ALCPatients with ALC < 300/µL were excluded from the JULIET trial (DLBCL)

Trial exclusion contextActive CNS disease was also an exclusion in JULIET and ELIANA (per trial definitions)

Implication for screeningConsider documenting ALC and CNS assessment during screening per trial precedents

Provider Actions & Requirements

Prior Authorization

Prior Authorization Required; Documentation Required

Prior authorization is required. Provider must submit documentation (e.g., office chart notes, laboratory results, imaging, pathology reports, treatment history) supporting that the member has met all approval criteria. All requests reviewed under this policy require medical director review.

Include documentation of diagnosis and indication (e.g., B-cell precursor ALL, LBCL, FL)
Provide recent (within 30 days) relevant laboratory data (e.g., ALC, CD3/T‑cell count when applicable)
Attach prior treatment records, chemotherapy regimen details, dates, and responses
If applicable, include documentation of prior stem cell transplantation (type and date)
Confirm member has not previously received CAR T‑cell therapy and Kymriah is not prescribed concurrently with other CAR T therapies
Requests for patients with active or primary CNS disease for LBCL will not be authorized (see Appendix D)

Documentation Required

Prior Systemic Therapy Requirement & Prior Lines Documentation

For LBCL and FL, members must have prior lines of systemic therapy as specified below. Prior lines of therapy must be documented in the medical record (regimens, agents, dates, and response). For Philadelphia chromosome–positive (Ph+) ALL, prior systemic therapy documentation must show two lines of chemotherapy that included two tyrosine kinase inhibitors.

LBCL: Relapsed or refractory after ≥2 lines of systemic therapy that includes rituximab and an anthracycline-containing regimen; alternatively, disease relapsed >12 months after completion of first-line therapy with partial response following second-line therapy (NCCN-supported off-label scenario) — document each prior line
FL: Relapsed/refractory after ≥2 lines of systemic therapy that include an anti‑CD20 monoclonal antibody (e.g., rituximab, obinutuzumab) plus an alkylating agent (e.g., bendamustine, cyclophosphamide) — document each prior line
Ph+ ALL: Member has received two lines of chemotherapy that included two different TKIs (e.g., imatinib, dasatinib, nilotinib, ponatinib, bosutinib) — document agents and lines

Documentation Required

Provider Actions — Prior Lines of Therapy Documentation

Provider must submit supporting clinical documentation demonstrating prior lines of therapy and eligibility criteria specific to the requested indication. Examples of acceptable documentation include office notes, infusion or chemotherapy administration records, operative reports, pathology reports, imaging, and laboratory values.

For ALL: documentation of CD19 tumor expression; leukapheresis eligibility (ALC ≥ 500/µL and, when ALC borderline, CD3 count ≥150/µL) per manufacturer guidance
For LBCL and FL: detailed prior therapy history with dates, agents, and responses; documentation that member does not have active or primary CNS disease when applicable (see Appendix D)
For transplant history: specify autologous vs allogeneic SCT and dates; members relapsed following allogeneic SCT must be ≥6 months from SCT at time of infusion (when applicable)
Show that member has not previously received CAR T‑cell therapy (list prior CAR‑T agents if applicable)

Background

Tisagenlecleucel (Kymriah) is an autologous, CD19-directed CAR T-cell immunotherapy approved for: pediatric B-cell precursor acute lymphoblastic leukemia (ALL) up to age 25 that is refractory or in second or later relapse, adult relapsed or refractory large B‑cell lymphoma (LBCL) after ≥2 prior lines of systemic therapy, and adult relapsed or refractory follicular lymphoma (FL) after ≥2 prior lines. Kymriah is not indicated for primary CNS lymphoma, and efficacy in patients with active CNS disease has not been established; patients with active CNS involvement were excluded from pivotal trials. The product is available only through the Kymriah REMS program and carries risks including cytokine release syndrome and neurological toxicities that require monitoring and management.

Definitions

ALC — definition

ALCabsolute lymphocyte count

ContextUsed as a screening and eligibility laboratory parameter for leukapheresis and dosing decisions

Acronym sourceAppendix A: Abbreviation/Acronym (policy appendices)

CAR — definition

CARchimeric antigen receptor

ContextRefers to the engineered receptor on T cells (CAR T-cell therapy) used in tisagenlecleucel

Acronym sourceAppendix A: Abbreviation/Acronym (policy appendices)

CNS — definition

CNScentral nervous system

ContextReferenced in exclusions and trial definitions (active CNS disease may exclude patients)

Acronym sourceAppendix A: Abbreviation/Acronym (policy appendices)

Active CNS disease — definition and implications

Active CNS diseaseActive CNS involvement by malignancy (trial-defined; e.g., CNS-3 per NCCN for ALL) — considered exclusion in several trials and the policy for LBCL

Trial definitionsELIANA defined active CNS involvement by CNS-3 (WBC ≥ 5/mcL in CSF with lymphoblasts); JULIET assessed by clinical symptoms, imaging, and CSF cytology if indicated

Policy implicationActive or primary CNS disease is a disqualifying condition for LBCL per policy Appendix D

Line of Therapy

salvage

salvage criteria: Salvage indications include: LBCL — relapsed or refractory after ≥2 lines of systemic therapy (including rituximab and an anthracycline) ; FL — relapsed or refractory after ≥2 lines including an anti‑CD20 plus an alkylating agent; ALL — refractory disease or in second or later relapse.

first-line | second-line | salvage

Line of therapy notes: Policy requires documentation of prior lines of therapy where specified by indication (examples: Ph+ ALL — two lines including two tyrosine kinase inhibitors; FL and LBCL — relapsed/refractory after ≥2 prior systemic therapies per indication and NCCN compendium).

Refer to the full policy for exact definitions of prior lines and acceptable regimens

Biomarker Requirements

CD19 — biomarker requirement

CD19 tumor expression requirement (ALL)Documented CD19 tumor expression is required for B-cell precursor ALL coverage

DocumentationProviders should include evidence of CD19 expression in prior authorization documentation for ALL cases

Source contextCoverage criteria and dosing appendices list CD19 as the target antigen for tisagenlecleucel

CD19 — trial enrollment note (JULIET)

CD19 in JULIET trialEnrollment in the JULIET trial did not require CD19 positive tumor expression

Response subgroup analysisBest overall response rates were comparable between patients with unequivocal CD19 expression and those with low/negative CD19 expression in JULIET

ImplicationCD19 positivity may not have been mandated in some clinical trial enrollment, but policy requires documented CD19 for ALL coverage

Covered Regimens and Therapeutic Alternatives

Regimen / Agent	Notes / context
R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone)
Listed as a standard large B‑cell lymphoma regimen in appendices; dosing regimen varies (Appendix lists RCHOP under LBCL regimens).

Regimen / Agent	Notes / context
MINE + rituximab (mesna, ifosfamide, mitoxantrone, etoposide + rituximab)
Included in appendices as a listed regimen for lymphoma; dosing regimen listed as 'varies'.

Policy Summary

PayerCentene

PolicyTisagenlecleucel (Kymriah) - Clinical Policy

Policy CodePolicy CP PHAR.361

Change TypeNo material change

Effective DateDec 1, 2017

Next Review Date

Key ActionPrior authorization required with supporting documentation and medical director review; prescribed by or in consultation with an oncologist or hematologist.

SourceLink

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