Table 1 Clinical and pathologic features in individual patient disease courses.

From: Venetoclax treatment of patients with relapsed T-cell prolymphocytic leukemia

 

Patient 1

Patient 2a

Patient 3

Patient 4

Patient 5

Patient 6

Patient 7

Patient 8

Patient 9

Demographics, comorbidities, and disease characteristics

 Age (y) at Ven start and gender

62 M

49 M

61 F

75 F

63 F

63 F

73 M

71 F

59 F

 CIRS score

6

6

2

6

10

4

5

3

13

 CIRS organ systems

Vasc, Resp, UGI, LGI

Vasc, Resp, UGI

Resp, GU

Heart, Vasc, UGI

Heart, Vasc, Resp, Renal, Psych

Vasc, UGI

Vasc, UGI, ENT

Endo, MSK, Psych

Heart, Vasc, Resp, UGI, Endo, Psych

 Flow cytometry

CD4−/CD8+

CD4+/CD8−

CD4+/CD8+

CD4+/CD8−

CD4−/CD8−b

CD4+/CD8−

CD4+/CD8−

CD4+/CD8+

CD4+/CD8−

 Complex karyotype

No

NA

Yes

Yes

NA

Yes

NA

Yes

No

 FISH (% nuclei)

TRAD (68%), TCL1Ax3 (68.5%)

TCL1A (88.5%)

TCL1A (97%)

TCL1A (52.5%), TCLA1Ax3 (22.5%), TRAD (64%), TRADx1 (22%)

NA

TCL1A (39.5%)

TCL1A (60%)

TRAD (74%), trisomy 8 (56%)

TCL1 (44%)

 JAK mutations

JAK3 (pA573V), VAF 35%

NA

NA

NA

NA

NA

NA

JAK3 (pM511I), VAF 42%; JAK3 (pA572V), VAF 34%

NA

 Prior lines of therapy

alemtuz, HDMTX + IT cytara, alemtuz + pentostatin, Flu + Mel + TBI + MUD HSCT

alemtuz, benda, benda

alemtuz + CTX + Flu + mitox, alemtuz, alemtuz + pentostatin, benda + vorinostat

alemtuz, benda, romidepsin

CHOP, gemcitabine + oxaliplatin, pralatrexate

CHOP, alemtuz,c romidepsin

alemtuz, BEAM + auto-HSCT

alemtuz

alemtuz

Clinical presentation at venetoclax start

 Months from diagnosis to Ven start

16

22

8

12

19

3

13

9

10

 Fatigue or B symptoms

None

None

Fatigue (PS 3)

Fatigue (PS 3)

Fatigue (PS 3) and B sx

Fatigue (PS 2)

Fatigue (PS 2)

B sx

Fatigue (PS 2)

 Extranodal sites

Cutaneous, ascites

None

None

None

Ascites

Cutaneous

Ascites

Pleural effusion

Cutaneous, ascites

 Spleen size (cm)

23

13.5

15.4

15

28

14.5

18

16

16

 Largest lymph node size (cm)

2.2

<1

<1

4.7

2.2

3.2

3.5

2.2

<1

 WBC (×109/L)

10.2

8.7

480.4

235.5

59.8

17.3

63.1

93.8

202.4

 LDH (U/L)

377

191

4236

4205

228

1659

2301

862

1947

 Hgb (g/dL)

9.4

14.1

6.3

6.9

9.5

12.3

6.7

9.3

10.0

 Platelets (×109)

31

96

10

41

80

190

47

84

73

 Bone marrow involvement (%)

90

NA

90

NA

30

10

60

NA

60

Venetoclax treatment details and outcomes

 Max Ven dose (mg)

50

200

200d, e

100d, e

800d

800d

400

800d

800d

 Ven duration (days)

25

42

4

4

171

30

177

201

101

 Concomitant steroids at Ven start

None

None

MP 2 g × 2d, 1 g × 3d

MP 500 mg × 1d, 1 g × 1d, 2 g × 1d

None

MP 250 mg × 5d

MP 1 g × 2d, 500 mg × 1d

MP 2 g × 3d

MP 1 g × 2d

 Overlapping benda

90 mg/m2

1 cycle

None

None

None

None

100 mg/m2

1 cycle

70 mg/m2

4 cycles

60 mg/m2

1 cycle

50–70 mg/m2

3 cycles

 Ven best response

PD

PD

PD

PD

SD

PR

PR

PR

PR

 Subsequent therapies

None

benda

brentuximab vedotin

None

None

None

alemtuz + cladribine + vorinostat

None

alemtuz + pentostatin

 Survival from Ven start (days)

30

53

6

4

464

34

200

201

120

  1. Alemtuz alemtuzumab, auto autologous, BEAM carmustine, etoposide, cytarabine, melphalan; benda: bendamustine, CIRS Cumulative Illness Rating-Scale, CHOP cyclophosphamide, doxorubicin, vincristine, prednisone, CTX cyclophosphamide; cytara: cytarabine, d days, Dx diagnosis, FISH fluorescence in situ hybridization, Flu fludarabine, HDMTX high-dose methotrexate, Hgb hemoglobin, HSCT hematopoietic stem cell transplantation, g grams, LN largest lymph node by imaging, Mel melphalan, mg milligrams, mitox mitoxantrone, MP methylprednisolone, MUD matched unrelated donor allogeneic, ND not done, PD progressive disease, PR partial remission, PS ECOG performance status, Pt patient, S sex, SD stable disease, TBI total body irradiation, TCL1A 14q32, TRAD 14q11.2, VAF variant allele frequency, Ven venetoclax, y years.
  2. aPatient was in PR following prior line 6 cycles bendamustine; all other patients actively progressing at Ven start.
  3. bAlthough CD4−/CD8− is a rare immunophenotype in T-PLL, the additional immunophenotype (CD1a−, CD16−, CD56−, and CD57−) and morphological (marked nuclear irregularity and distinct nucleoli) findings in combination with the clinical presentation were considered most consistent with a diagnosis of T-PLL.
  4. cAlemtuzumab subcutaneous. All of the other patients treated with alemtuzumab received intravenous alemtuzumab.
  5. dUnderwent venetoclax rapid dose escalation.
  6. ePatient receiving concurrent CYP3A4 inhibitor (pt #3: posaconazole; pt#4 diltiazem).
Back to article page