In a patient with relapsed diffuse large B‑cell lymphoma receiving polatuzumab‑vedotin and mosunetuzumab plus vincristine who presents with persistent dilated colon and profuse diarrhea, what is the likelihood that this is due to cytomegalovirus (CMV) colitis and what is the recommended antiviral treatment?

CMV Colitis is Highly Likely in This Clinical Scenario and Requires Immediate Antiviral Treatment

In a patient with relapsed DLBCL receiving polatuzumab vedotin, mosunetuzumab, and vincristine who presents with persistent dilated colon and profuse diarrhea, CMV colitis should be strongly suspected and treated empirically with ganciclovir while awaiting tissue confirmation.

Understanding the Risk in This Patient

This patient faces exceptionally high risk for CMV reactivation due to multiple converging factors:

Immunosuppression from Novel Therapies

The combination therapy creates profound immunosuppression through several mechanisms:

• Mosunetuzumab (CD3×CD20 bispecific antibody) causes T-cell engagement and potential exhaustion, particularly with prolonged use 1
• Polatuzumab vedotin contributes to immunosuppression, though specific CMV risk data are limited 2, 3
• Vincristine adds to the immunosuppressive burden
• The NCCN guidelines specifically note that patients receiving T-cell-engaging antibodies require CMV monitoring per institutional guidelines 4

Clinical Presentation Strongly Suggests CMV

The combination of dilated colon with profuse diarrhea in this immunocompromised setting is highly characteristic of CMV colitis:

• CMV preferentially affects the colon in immunosuppressed patients, causing tissue-invasive disease 5
• Dilated colon suggests severe colonic involvement
• Profuse diarrhea is a cardinal manifestation

Diagnostic Approach

Immediate tissue diagnosis is essential but should not delay treatment:

Obtain Colonic Biopsies Urgently

• Immunohistochemistry (sensitivity 93%, specificity 92-100%) is the preferred diagnostic method 6
• Tissue PCR (sensitivity 65-100%, specificity 40-100%) as complementary testing 6
• Look for CMV inclusions on H&E staining 5

Blood Testing Has Limited Value

• Serum PCR and CMV viremia have poor sensitivity for diagnosing CMV colitis, though specificity is high 6
• Blood tests should not be used to rule out CMV colitis 5

Treatment Strategy

Initiate Antiviral Therapy Immediately

Do not wait for tissue confirmation in this high-risk patient with severe symptoms:

• Intravenous ganciclovir 5 mg/kg twice daily for 5-10 days 5
• Transition to valganciclovir 900 mg daily to complete a 2-3 week course 5
• Earlier transition to oral therapy is acceptable depending on clinical response 5

Critical Management of Immunosuppression

This is where management becomes nuanced:

For localized CMV colitis (no systemic dissemination):

• Steroids should be tapered if the patient is receiving them 5
• Consider maintaining other immunosuppression while treating CMV, as many case series show successful outcomes with continued immunosuppression plus antivirals 5
• The lymphoma treatment may need to continue given the aggressive nature of relapsed DLBCL

For systemic/disseminated CMV infection:

• Discontinue ALL immunosuppressive therapy immediately 5
• Look for signs of CMV syndrome: fever, malaise, leukopenia, thrombocytopenia, elevated liver enzymes 5
• Check for end-organ involvement (pneumonitis, hepatitis, encephalitis)

Monitor for Treatment Complications

Ganciclovir toxicity overlaps with CMV manifestations:

• Neutropenia and thrombocytopenia are common side effects 5
• These can also be manifestations of systemic CMV
• Requires multidisciplinary approach with infectious disease specialists 5

Alternative for ganciclovir intolerance:

• Foscarnet for ganciclovir-intolerant patients or resistant CMV 5
• Requires strict monitoring of renal function and electrolytes
• Administer normal saline to reduce irreversible renal damage risk 5

Critical Pitfalls to Avoid

Do Not Rely on Blood Tests Alone

The biggest mistake would be ruling out CMV colitis based on negative serum PCR—tissue diagnosis is mandatory 6.

Do Not Automatically Stop All Immunosuppression

Unlike systemic CMV disease, localized CMV colitis may be managed with continued immunosuppression plus antivirals 5. The decision depends on:

• Severity of colonic involvement
• Presence of systemic symptoms
• Viral load in tissue
• Need to control underlying lymphoma

Consider the Lymphoma Treatment Urgency

This patient has relapsed DLBCL, an aggressive malignancy. The balance between treating CMV and controlling lymphoma is delicate:

• Complete cessation of lymphoma therapy may allow rapid disease progression
• Work closely with oncology to determine if brief treatment interruption is feasible
• Some patients achieve CMV clearance while continuing immunosuppression 5

Prognosis and Monitoring

Patients with low viral load and few IHC-positive cells may clear CMV without antivirals, but given this patient's severe symptoms, treatment is mandatory 5.

The higher the colonic viral load, the higher the risk of complications, supporting aggressive antiviral therapy 5.

Monitor response with:

• Clinical improvement in diarrhea
• Repeat colonoscopy if symptoms persist
• Consider repeat tissue testing to document clearance

Special Considerations for T-Cell-Engaging Therapies

The use of mosunetuzumab creates unique risks:

• T-cell exhaustion may impair CMV-specific immunity 1
• Risk increases with prolonged use of T-cell-engaging antibodies 1
• Prophylactic strategies are not well-established for these novel agents, but monitoring is recommended 4

The combination of consecutive T-cell-directed therapies (if this patient previously received CAR-T) further amplifies CMV risk 1.