U.S. Food and Drug Administration (FDA)-Approved Indications

Columvi is indicated for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy.

Compendial Uses

B-Cell Lymphomas

Diffuse Large B-Cell Lymphoma

High Grade B-Cell Lymphoma

Histologic Transformation of Indolent Lymphoma to Diffuse Large B-Cell Lymphoma

Human Immunodeficiency Virus (HIV)-Related B-Cell Lymphoma

HIV-Related Diffuse Large B-cell Lymphoma

Primary Effusion Lymphoma

Human Herpes Virus Type 8 (HHV8)-Positive Diffuse Large B-cell Lymphoma

Monomorphic Post-Transplant Lymphoproliferative Disorder

Glofitamab-gxbm is available as Columvi (Genentech, Inc.) and is a recombinant humanized anti-CD20 anti-CD3ɛ bispecific immunoglobulin G1 (IgG1) monoclonal antibody. By functioning as a CD20-directed CD3 T-cell engager, Columvi binds to CD20 and to CD3 receptor expressed on the surface of B cells and T cells, respectively. Columvi targets both T cells and B cells, where the T-cell engaging bispecific antibody activates the T cell proteins to kill cancer cells on the B cell. Columvi showed anti-tumor activity in vivo in mouse models of DLBCL (Genentech, 2023).

According to the prescribing information, Columvi carries a black box warning for cytokine release syndrome (CRS), including serious or fatal reactions, which can occur in patients receiving Columvi. Patients should premedicate before each dose, and initiate treatment with the Columvi step-up dosing schedule to reduce the risk of CRS. Withhold Columvi until CRS resolves or permanently discontinue Columvi based on severity.

Per the prescribing information, Columvi carries the following warnings and precautions:

Neurologic toxicity: Can cause serious neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS). Monitor for neurologic toxicity; withhold or permanently discontinue based on severity.

Serious infections: Can cause serious or fatal infections. Monitor for signs and symptoms of infection and treat appropriately.

Tumor flare: Can cause serious tumor flare reactions. Monitor for risk for complications of tumor flare.

Embryo-fetal toxicity: May cause fetal harm. Advise females of reproductive potential for the potential risk to the fetus and to use effective contraception.

Columvi carries the following adverse reactions:

Adverse reactions (≥ 20%), excluding laboratory abnormalities: Cytokine release syndrome, musculoskeletal pain, rash, and fatigue.

Grade 3 to 4 laboratory abnormalities (≥ 20%): Lymphocyte count decreased, phosphate decreased, neutrophil count decreased, uric acid increased, and fibrinogen decreased.

On June 15, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to glofitamab-gxbm (Columvi) for relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL) arising from follicular lymphoma, after two or more lines of systemic therapy. The FDA approval was based on supporting data from the NP30179 study (FDA, 2023).

The NP30179 study, an open-label, multicenter, multicohort, single-arm clinical trial, included patients with relapsed or refractory LBCL after two or more lines of systemic therapy. Patients received pretreatment with obinutuzumab on cycle 1 day 1 followed by Columvi via intravenous infusion, starting with a 2.5 mg step-up dose on cycle 1 day 8, followed by a 10 mg step-up dose cycle 1 day 15, then 30 mg on cycle 2 day 1 and on day 1 of each subsequent cycle. The cycle length was 21 days and Columvi was administered for up to 12 cycles unless patients experienced disease progression or unacceptable toxicity. The efficacy evaluation population consisted of 132 patients with de novo DLBCL, NOS (80%) or LBCL arising from follicular lymphoma (20%) who received at least one dose of Columvi. The primary efficacy outcome measures were objective response rate (ORR) and duration of response (DOR), determined by an Independent Review Committee using the 2014 Lugano criteria. The ORR was 56% (95% confidence interval [CI]: 47, 65) with 43% achieving complete responses. The estimated median follow-up was 11.6 months among responders and the estimated median DOR was 18.4 months (95% CI: 11.4, not estimable). The 9-month Kaplan-Meier estimate for DOR was 68.5% (95% CI: 56.7, 80.3). The median time to response was 42 days (FDA, 2023; Genentech, 2023).

Note

: Requires Precertification:

Precertification of glofitamab-gxbm (Columvi) is required of all Aetna participating providers and members in applicable plan designs. For precertification of glofitamab-gxbm (Columvi),

call (866) 752-7021 (commercial), or fax (888) 267-3277. For Statement of Medical Necessity (SMN) precertification forms, see Specialty Pharmacy Precertification .

For Medicare Part B plans, call (866) 503-0857, or fax (844) 268-7263.

Criteria for Initial Approval

B-cell Lymphoma

Aetna considers glofitamab-gxbm (Columvi) medically necessary for treatment of B-cell lymphoma after at least 2 prior lines of systemic therapy when the member has partial response, no response, progressive, relapsed or refractory disease and

both

of the following criteria are met:

The member has

any

of the following subtypes:

Diffuse Large B-Cell Lymphoma (DLBCL);

or

High Grade B-Cell Lymphoma as a single agent;

or

Histologic Transformation of Indolent Lymphoma to DLBCL;

or

HIV-Related B-Cell Lymphoma including HIV-related DLBCL, primary effusion lymphoma, and HHV8-positive DLBCL, not otherwise specified as a single agent;

or

Monomorphic Post-Transplant Lymphoproliferative Disorder as a single agent;

and

The member will be pretreated with a single dose of obinutuzumab (Gazyva) 7 days before initiation with the requested medication.

Aetna considers all other indications as experimental and investigational.

Continuation of Therapy

Aetna considers continuation of glofitamab-gxbm (Columvi) therapy (up to a maximum of 12 cycles) medically necessary for members requesting reauthorization for an indication listed in Section I when there is no evidence of unacceptable toxicity or disease progression while on the current regimen.

Dosage and Administration

Glofitamab-gxbm is supplied as Columvi injection, for intravenous use, in the following dosage forms and strengths:

2.5 mg/2.5 mL (1 mg/mL) in a single-dose vial

10 mg/10 mL (1 mg/mL) in a single-dose vial.

Relapsed or refractory diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS) or large B-cell lymphoma (LBCL):

Pretreat with a single 1,000 mg dose of obinutuzumab intravenously 7 days before initiation of Columvi (cycle 1 day 1).

Administer premedications as recommended.

Administer only as an intravenous infusion.

Recommended dosage:

Table: Recommended Dosage Treatment Cycle Footnote1 * Day Dose of Columvi Cycle 1 Day 1 Obinutuzumab 1,000 mg Day 8 Step-up dose 1 2.5 mg Day 15 Step-up dose 2 10 mg Cycle 2-12 Day 1 30 mg Footnote1

*Cycle = 21 days

Administer in a facility equipped to monitor and manage cytokine release syndrome (CRS).

Individuals should be hospitalized for the 2.5 mg step-up dose and for subsequent infusions as recommended.

Refer to full prescribing information for Columvi for instructions on preparation, administration, and dosage modifications for adverse reactions.

Source: Genentech, 2023