Primary Mediastinal B-Cell Lymphoma

beau hilton, 2023-12-15

Primary Mediastinal B-Cell Lymphoma

beau hilton, 2023-12-15

Presentation

35M, athlete, no known medical problems.

(all dates modified for HIPAA, relative time spans preserved for instruction)

2023-04-15: Working in the crawl space under his house, developed progressive and eventually severe L arm pain and swelling.

Went to local ED: LUE DVT, put on rivaroxaban. CTPE: +supraclav LN, o/p f/u recommended.

2023-04-20: Called 911 for dyspnea.

2023-04-21: OSH obtained cervical LN core bx: paracortical hyperplasia w focal necrosis

2023-05-05: OSH ER for f/ns and arthralgia, given amox x5d

2023-05-10: Our ER for f/c/ns/n/v, weight loss, chest pain, HA, pruritus.

CT chest: +mediastinal mass, SVC compression w/o critical stenosis, R pleural effusion

CT

https://radiopaedia.org/cases/8655

Presentation continued

2023-05-15: core bx of mediastinal LN done

2023-05-16: feeling much better (fluids and other supportive care), d/c home

2023-05-17: bx resulted as large B-cell neoplasm. Primary team notified him, he was doing ok and o/p f/u scheduled already for next week, so deferred readmission.

Office visit and admission

2023-05-24: HR 130s, dyspneic, plethoric, but able to get around w/o assistance and speak in complete sentences.

Discussed DLBCL vs PMBCL, possibility of cure in either case, recommended admission for expedited w/u and tx start.

Contacted thoracic team for mediastinoscopy, which they accommodated same-day (+chest tube).

Mostly fibrotic tissue, "like chopping through wood".

Wrote for R-EPOCH to start next day.

Admission continued

FDG-PET CT: 9.4x6.3cm mediastinal mass, LAD, diffuse axial skeleton uptake (hyperplasia vs infiltration)
BMBx: NED
Mediastinal bx: results came back a few days later, mostly fibrosis, crush artifact, necrosis
- mature B-cell markers: CD20+, CD45+, PAX5+.
- PMBCL: CD23 patchy ( -ve in DLBCL, cHL, MGZL), CD30 patchy (30% DLBCL, but weak+ in most PMBCL), CD10- (nonGC), equivocal [BCL2/6, c-MYC, MUM1], EBER-
SVC syndrome: much back and forth re SVC stent, RT.
- Ultimately pursued neither, sx slowly improved.

Subsequent cycles

C2: dose level +0
- (late onset severe neutropenia - ?GCSF)
C3: dose level +1
Interval FDG-PET CT: "near complete resolution" (tiny remnant FDG+, ?malignant vs reactive)
C4: dose level +0 (late onset severe neutropenia)
C5: dose level +1
C6: dose level +2
EOT FDG-PET: next week!

Questions

How common is it and who gets it?
What is the typical presentation?
What are the key parts of the workup?
How common are nondiagnostic biopsies?
What are the key parts of treatment?
What is the role of radiotherapy?
How should we approach post-treatment surveillance?
What are the long-term adverse effects of surviving therapy?

Epidemiology

2-4% of all NHL (SEER 2023 estimate 80,550 NHL * 2% = ~1600-3200/yr)¹
~60% female²
median age 30-35^2,3

S/sx prevalence at presentation (~%)

Tumor size ≥10cm¹	60
Clinical SVC syndrome¹	55
Radiographic SVC compromise¹	80
Pleural effusion²	50
VTE³	35
B symptoms⁴	30-50

Selected clinicopathological features (~%)

Bone marrow involvement¹	2
CNS involvement²	5-10
Marked fibrosis¹	25

Management

Cancer 1988: CHOP21 + 40Gy RT.

NEJM 2013: DA-R-EPOCH.

Management

NEJM 2013: DA-R-EPOCH.

BJH 2018: R-CHOP vs DA-R-EPOCH.

Monitoring

NEJM 2013: DA-R-EPOCH.

NEJM 2013: No increased cardiotoxicity.

Future directions

PD-L1++
- KEYNOTE-170
  - pembro monotherapy for R/R PMBCL
  - N=53, median LoT 3 (26.4% ASCT)
  - ORR 41.5%, CR 20.8%, mOS 22.3mo, 4y OS 45.3%
- –> frontline chemo + pembro
  - NCT04759586 (investigator’s choice + pembro)
Cellular therapy
- e.g. ZUMA-1
  - axi-cel CAR-T
  - N=101, R/R LCL, 8% PMBCL
  - ORR 83%, CR 58%, mOS 25.8mo, 5y OS 42.6%

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