Table 1.
Clinical and biological characteristics of CLL samples collected from seven patients (CLL1-7) prior to venetoclax therapy.
| Sample ID | Gender | IGHV status (%) | IGHV gene | FISH (%) | Karyotype | List of all therapies prior venetoclax | Age at CLL DX | SC2 time point from Venetoclax start date (yrs) | % increase in MRD at SC2 from lowest detectable MRD achieved | Time on venetoclax therapy (yrs) | Type of venetoclax therapy |
|---|---|---|---|---|---|---|---|---|---|---|---|
| CLL1 | Male | U-IGHV (100%) | IGHV3-48 | normal | Abnormal: 46, XY, t(1;14)(q42;q32)[cp8]/46,XY[12] | (1) FCR, (2) Campath, (3) HDMP, (4) Campath | 48.3 | 5.2 | 50 | 6.4 | Venetoclax alone |
| CLL2 | Female | U-IGHV (100%) | IGHV1-69 | tri 12 (53%) | Abnormal: 47, XX, +12[13]/47, idem, del(8)(p11.2)[3] | (1) FR, (2) Revlimid+Rituximab, (3) Revlimid Consolidation, (4) Ofatumumab, (5) Ibrutinib | 63.1 | 1.1 | 30 | 1.2 | Venetoclax alone |
| CLL3 | Male | U-IGHV (99.7%) | IGHV1-69 | 13q del (11.5%), 17p del (11.5%) | Complex: 46, XY, del(13)(q12q14)[2]/43, X, −Y, add(1)(q42), add(4)(?q25q31), del(12)(p13), −13, der(17)t(17;18)(p11.2; q11.2), −18[1]/46,XY[17] | (1) Ad-ISF35 Intranodal Injection + FCR | 55.4 | 4.9 | 49 | 6.5 | Venetoclax + anti-CD20 |
| CLL4 | Male | U-IGHV (100%) | IGHV1-2 | 13q del (64%), 17p del (70%) | Complex: 46, XY, del(13)(q13q14)[1]/46, idem, add(2)(p13), del(7)(q?34q36), −8, der(15)t(8;15)(q?21; p11.2), del(17)(p12), +mar[cp7]/46, idem,der(7)t(7; 12)(q22; q24.1), der(12)add(12)(p12)t(7; 12)(q22; q24.1)[cp7]/46, XY[7] | (1) FC, (2) HDMP, (3) Ibrutinib | 67.6 | 0.7 | 1 | 0.7 | Venetoclax alone |
| CLL5 | Female | U-IGHV (100%) | IGHV3-33 | 13q del (10%), 17p del (8%) | Complex: 45, XX, del(1)(q42), add(4)(p15), del(6)(q21), −8, add(10)(p?13), −13, del(17)(p13), add(18)(q12), +mar[cp8]/46,XX[14] | (1) FCR, (2) AVL-292, (3) Ibrutinib | 52.6 | 1.8 | 83 | 1.8 | Venetoclax alone |
| CLL6 | Male | U-IGHV (99.7%) | IGHV1-69 | 11q del (56%), 17p del (59%) | Complex: 46, XY, t(8; 9)(q24;q22), ?11q[3]/45, der(8)t(8;9)(q24; q22), −9, ?11q, der(17)t(9; 17)(p?13;p11.2)[10]/46,XY[9] | (1) Revlimid+Rituximab, (2) HDMP+Ofatumumab, (3) Revlimid+Rituximab, (4) Ublituximab + Ibrutinib, (5) Ibrutinib | 56.3 | 1.4 | 40 | 1.5 | Venetoclax alone |
| CLL7 | Male | M-IGHV (97.9%) | IGHV3-21 | 13q del (23%), 11q del (6%), 17p del (16%) | Complex: 45, XY, del(9)(p?21), der(9)t(9; 21)(?q11;?q11), del(17)(p11.2), −21[3]/44, idem, −5, add(14)(p11.2)[4]/46,XY,del(11) (?q22q25)[4]/nonclonal abnormality[1]/46, XY[14].nuc ish(ATMx1)[11/200], (CCND1,IGH)x2[200], (D12Z3x2) 200], (D13S319x0)[46/200], (LAMP1x2)[200], (TP53x1)[31/200] | (1) FCO, (2) Navitoclax + BR, (3) Obinutuzumab | 58.5 | 2.8 | 49 | 3.8 | Venetoclax alone |
Percent (%) increase in MRD at SC2 from lowest detectable MRD achieved calculated with the formula 100 x [(Log10(%MRD x ALC at SC2) - [(Log10(%MRD x ALC at 12 months)/[(Log10(%MRD x ALC at 12 months). FCR Fludarabine+Cyclophosphamide+Rituximab, FR Fludarabine+Rituximab, HDMP High Dose Methylprednisolone, AVL-292: Btk inhibitor, FC Fludarabine+Cyclophosphamide, BR Bendamustine+Rituximab, FCO Fludarabine+Cyclophosphamide+Ofatumumab.