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| Clinical characteristics | Patient 1 | Patient 2 | Patient 3 | Patient 4 |
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| Age/sex | 70s/M | 60s/F | 90s/F | 60s/M |
| Initiation of antilymphoma treatment | First line: rituximab and acalabrutinib | First line: ibrutinib and rituximab | Acalabrutinib | 1st line: VDR
2nd line: ibrutinib + rituximab |
| Clinical presentation leading to the diagnosis | Symptomatic hepatomegaly, diastolic CHF | Stage IV CKD, anemia, no significant proteinuria | Transfusion dependent anemia, CHF, stage IV CKD | Dyspnea on exertion, lymphadenopathy |
| Circulating monoclonal protein (g/dL) | IgM kappa, M spike 2.6 | IgM lambda, M spike 0.4 | IgM kappa, M spike 2.2 | IgM lambda, M spike 4 |
| IgM (40–230 mg/dL) | 2666 | 452 | 2949 | 8020 |
| Serum-free kappa (3.30–19.40 mg/L) | 205 | 30 | 705 | 7 |
| Serum-free lambda (5.7–26.3 mg/L) | 3 | 39 | 101 | 170 |
| Kappa to lambda ratio | 68 | 0.81 | 7 | 0.04 |
| dFLC at presentation | 202 | 9 | 604 | 163 |
| Troponin T (0.000–0.029 ng/mL) | 0.042 | Not tested | 0.1 | 0.047 |
| NT-proBNP (0–450 pg/mL) | 4928 | 650 | 10500 | 2300 |
| Cardiac modified Mayo stage (2015) | IIIa | N/A | IIIb | IIIa |
| Serum albumin (3.6–5.1 g/dL) | 4.2 | 3.9 | 3.1 | 3.9 |
| Creatinine (0.58–0.96 mg/dL) | 1 | 2.41 | 2.5 | |
| Cholesterol (normal is <200 mg/dL) | 182 | 198 | 185 | 144 |
| Alkaline phosphatase (33–130 U/L) | 407 | 99 | 75 | |
| 24-hour urinary protein (normal is <200 mg) | 150 | 191 | 99 | 130 |
| ECHO findings | Grade III left ventricular diastolic dysfunction, LVEF 48%, mild upper septal left ventricular hypertrophy | Normal LV and RV, LVEF 58%, grade I left ventricular diastolic dysfunction | Grade II left ventricular diastolic dysfunction, LVEF 28%, there is mild upper septal left ventricular hypertrophy | Grade III left ventricular diastolic dysfunction, LVEF 57%, RVH and LVH, advanced cardiac amyloidosis with restrictive physiology, sparkling granular appearance, and apical sparing |
| Tissue biopsy confirming the diagnosis of AL amyloidosis | Liver, bone marrow, and cardiac biopsy | Renal biopsy | Bone marrow biopsy | Lymph node biopsy showing both LPL and amyloid |
| LC-MS/MS analysis | The main amyloidogenic component is kappa immunoglobulin light chains | The main amyloidogenic component is lambda immunoglobulin light chains | Amyloid type confirmed with immunohistochemistry | Amyloid type confirmed with immunohistochemistry |
| Bone marrow biopsy findings | 40–50% involvement by LPL, amyloid + | 50% involvement by LPL, amyloid − | 90% involvement by LPL, gain of chromosomes 4 and 18 | Not done |
| MYD88 status | Mutated | Mutated | Mutated | Mutated |
| Complications during treatment with BTK-I and rituximab | Rituximab flare, thumb hematoma (Figure 4) leading to 50% dose reduction of acalabrutinib | None | None | Atrial fibrillation leading to discontinuation of ibrutinib |
| Antilymphoma therapy prior to initiating BTK inhibitor-based regimen | None | None | Intolerance to rituximab and bortezomib | First line (11/2016–3/2017): VDR with PR
2nd line (4/2017–12/2017): ibrutinib + rituximab with VGPR
3rd line (1/2018–6/2018): BR with stable disease
4th line: antiamyloid fibril MAB + CyBorD in a clinical trial with VGPR |
| Best hematologic response/outcome with BTK inhibitor therapy/time to response | VGPR with hepatic and cardiac response/8 months | CR/12 months | VGPR/10 months | CR/9 months |
| Organ response/time to response | Cardiac/hepatic response/6 months | Stable disease without renal progression to date | Cardiac response/6 months
Stable disease without renal progression | Cardiac response/6 months |
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