Table 1.
Baseline demographics, disease characteristics, treatment, clinical outcomes, and toxicities for three patients with relapsed/refractory Waldenström macroglobulinemia treated with CAR Tcell therapy
| Baseline patient characteristics | Patient 1 | Patient 2 | Patient 3 |
| Age, gender | 73, female | 75, female | 64, female |
| Genotype | MYD88 p.L265P CXCR4 p.S342fs TP53 p.R175H/R196Q |
MYD88 p.L265P Loss of MYB and ATM by FISH |
MYD88 p.L265P DNMT3A p.R823K |
| Time from diagnosis to CAR T | 12.1 years | 10.4 years | 10.2 years |
| Prior lines of therapy (best response by IWWM criteria) | Rituximab (PR) Rituximab+Fludarabine (PR) Rituximab+Bendamustine (VGPR) Duvelisib (NE) Ibrutinib (PD) BDR ->R-Bortezomib maint (MR) IMO-8400 (TLR antagonist) (NE) Ofatumumab+Bendamustine (MR) |
Rituximab (PR) Rituximab+Bendamustine (PR) BDR (PR) Venetoclax (MR) Ibrutinib (PR) Ibrutinib/Ofatumumab (PD) |
Rituximab+Bortezomib (PR) Rituximab+Bendamustine (PR) Ibrutinib (PD) Ofatumumab+Cyclophosphamide + Fludarabine (CR, MRD +on BM) Ofatumumab (PD) |
| Marrow involvement | Hypercellular marrow (80%) LPL involvement (50%) |
Hypercellular marrow (70%) LPL involvement (40%–60%) |
Hypercellular marrow (95%) LPL involvement (70%–80%) |
| Transfusion dependence | Pancytopenic, requiring PRBC and platelet transfusions multiple times per week | Anemia requiring transfusions | No |
| Pretreatment IgM | 2570 mg/dL | 3789 mg/dL | 7520 mg/dL |
| Treatment | |||
| CAR-T product | CD19-CD28-CD3ζ (19-28z) | CD19-CD28-CD3ζ (19-28z) | CD19-CD28-CD3ζ (19-28z) plus 4-1BBL (armored CAR product) |
| Bridging therapy | Bendamustine | Ibrutinib | Ofatumumab |
| Conditioning | Cyclophosphamide 1 g/m2 (day −3), Fludarabine 25 mg/m2 (day −3 to −1) |
Cyclophosphamide 1 g/m2 (day −3) Fludarabine 25 mg/m2 (day −3 to −1) |
Cyclophosphamide 300 mg/m2 (day −3 to −1) Fludarabine 30 mg/m2 (day −3 to −1) |
| CAR T cell dose | 1×106 CAR T cells/kg | 1×106 CAR T cells/kg | 1×105 CAR T cells/kg |
| Response | |||
| Best response | Stable disease by IgM Hematologic response |
PR | VGPR |
| Vital status | Deceased | Deceased | Alive |
| Cause of death | Disease | Sepsis 2/2 PsA bacteremia | N/A |
| PFS (months) | 6.8 | 4.0 | 26.5 |
| OS (months) | 12.4 | 4.0 | Not reached |
| Toxicity | |||
| CRS | Grade 1 | Grade 2 | Grade 2 |
| Neurotoxicity | None | None | Grade 2 |
| Infections | None | None | None |
| Other | Grade 2 peripheral edema Grade 2 nasal congestion Grade 2 anemia (baseline) Grade 1 rash (pityriasis rosacea) |
Grade 1 edema Grade 1 alopecia Grade 1 pleural effusion Grade 2 hypothyroidism |
Grade 2 dyspnea/wheezing Grade 2 elevated bicarbonate Grade 2 anemia Grade 1 diarrhea Grade 1 nausea |
BDR, bortezomib, dexamethasone, rituximab; CAR, chimeric antigen receptor; CR, complete response; CRS, cytokine release syndrome; IHC, immunohistochemistry; IWWM, International Workshop on Waldenström Macroglobulinemia; LPL, lymphoplasmacytic lymphoma; MRD, minimal residual disease; NE, response not evaluable; OS, overall survival; PFS, progression-free survival; PR, partial response; PRBC, packed red blood cells; PsA, pseudomonas aeruginosa; TLR, toll-like receptor; VGPR, very good partial response.