Methods of treating AL amyloidosis

1. A method of treating a patient having AL amyloidosis, comprising:

(a) determining:

(i) the Mayo Stage of the patient's AL amyloidosis;

(ii) the 6 minute walk distance (6MWD) and ejection fraction (EF) of the patient;

(iii) the Mayo Stage of the patient's AL amyloidosis and the EF of the patient; or

(iv) the Mayo Stage of the patient's AL amyloidosis, and the 6MWD and the EF of the patient; and

(b) selecting the patient for treatment with an antibody comprising a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 3, 4 and 5, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8 if the patient:

(i) has Mayo Stage IV AL amyloidosis;

(ii) has a 6MWD≥150 meters and an EF>50% at baseline;

(iii) has Mayo Stage IV AL amyloidosis and EF>50% at baseline; or

(iv) has Mayo Stage IV AL amyloidosis, a 6MWD≥150 meters and an EF>50% at baseline; and

(c) administering an effective dosage of the antibody to the selected patient.

2. The method of claim 1 , wherein the selected patient has Mayo Stage IV AL amyloidosis.

3. The method of claim 1 , wherein the selected patient has a 6MWD≥150 meters and an EF>50%.

4. The method of claim 2 , wherein the selected patient has an EF>50%.

5. The method of claim 4 , wherein the selected patient has a 6MWD≥150 meters.

6. The method of claim 1 , wherein the antibody is a humanized antibody.

7. The method of claim 1 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 1.

8. The method of claim 1 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 2.

9. The method of claim 1 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 1, and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 2.

10. The method of claim 1 , wherein the antibody is birtamimab.

11. The method of claim 1 , wherein the selected patient is newly diagnosed and AL amyloidosis treatment naïve.

12. The method of claim 1 , wherein the selected patient previously received or concomitantly receives administration of melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, doxorubicin, doxycycline, daratumumab, autologous transplant, or a combination thereof.

13. The method of claim 1 , wherein the selected patient previously received or concomitantly receives administration of Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD).

14. A method of treating a patient having AL amyloidosis, comprising:

(a) selecting a patient having AL amyloidosis for treatment with an antibody comprising a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 3, 4 and 5, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8 if the patient has:

(i) Mayo Stage IV AL amyloidosis;

(ii) a 6 minute walk distance (6MWD)≥150 meters and EF>50% at baseline;

(iii) Mayo Stage IV AL amyloidosis and an EF>50% at baseline; or

(iv) Mayo Stage IV AL amyloidosis and a 6MWD≥150 meters and EF>50% at baseline; and

(b) administering an effective dosage of the antibody to the selected patient.

15. The method of claim 14 , wherein the selected patient has Mayo Stage IV AL amyloidosis.

16. The method of claim 14 , wherein the selected patient has a 6MWD≥150 meters and an EF>50%.

17. The method of claim 15 , wherein the selected patient has a 6MWD≥150 meters and an EF>50%.

18. The method of claim 15 , wherein the selected patient has an EF>50%.

19. The method of claim 14 , wherein the antibody is a humanized antibody.

20. The method of claim 14 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 1.

21. The method of claim 14 , wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 2.

22. The method of claim 14 , wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 1, and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 2.

23. The method of claim 14 , wherein the antibody is birtamimab.

24. The method of claim 14 , wherein the patient is newly diagnosed and AL amyloidosis treatment naive.

25. The method of claim 14 , wherein the selected patient previously received or concomitantly receives administration of melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, doxorubicin, doxycycline, daratumumab, autologous transplant, or a combination thereof.

26. The method of claim 14 , wherein the selected patient previously received or concomitantly receives administration of Cyclophosphamide, Bortezomib and Dexamethasone (CyBorD).

27. A method of treating a patient with AL amyloidosis, comprising:

(a) selecting a patient with AL amyloidosis having a 6 minute walk distance (6MWD)≥150 meters and an ejection fraction (EF)>50% at baseline for treatment with an antibody comprising a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 3, 4 and 5, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8; and

(b) administering an effective dosage of the antibody to the selected patient.

28. A method of treating a patient with AL amyloidosis comprising:

(a) selecting a patient having AL amyloidosis for treatment with an antibody comprising a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 3, 4 and 5, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8, if the patient has Mayo Stage IV AL amyloidosis, a 6 minute walk distance (6MWD)≥150 meters, and an ejection fraction (EF)>50% at baseline; and

(b) administering an effective dosage of the antibody to the selected patient.

29. A method of reducing the risk of mortality in a patient with AL amyloidosis by at least 45%, comprising:

(a) selecting a patient having AL amyloidosis for treatment with an antibody comprising a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 3, 4 and 5, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8 if the patient has:

(i) Mayo Stage IV AL amyloidosis;

(ii) a 6MWD of greater than or equal to 150 meters and an EF of more than 50% at baseline, or

(iii) Mayo Stage IV AL amyloidosis and an EF of >50% at baseline; and

(b) administering an effective dosage of the antibody to the selected patient.

30. The method of claim 29 , wherein the risk of mortality is of all-cause mortality.

31. The method of claim 29 , wherein the risk of mortality is of cardiac mortality.

32. The method of claim 29 , wherein the antibody is birtamimab.

33. The method of claim 29 , wherein the effective dosage of the antibody is administered from a pharmaceutical formulation comprising the antibody at a concentration within the range from about 1 mg/mL to about 100 mg/mL.

34. The method of claim 29 , wherein the dosage is from about 0.5 mg/kg to about 30 mg/kg and the antibody is administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly.

35. The method of claim 33 , wherein the antibody is present at a concentration of about 50 mg/mL.

36. The method of claim 33 , wherein the dosage is about 24 mg/kg and the antibody is administered intravenously every 28 days.

37. The method of claim 29 , wherein the duration of the treatment is at least 9 months.

38. The method of claim 29 , wherein the duration of the treatment is at least 12 months.

39. The method of claim 29 , wherein the antibody is a Fab, Fab′, F(ab′)2, F(ab)c, Dab, nanobody, or Fv.

40. A method of improving a 6 minute walk distance (6MWD) in a patient having AL amyloidosis, comprising:

(a) selecting a patient having AL amyloidosis for treatment with an antibody comprising a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 3, 4 and 5, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8 if the patient has a 6MWD≥150 meters and EF>50% at baseline, and

(b) administering an effective dosage of the antibody to the selected patient.

41. The method of claim 40 , wherein the AL amyloidosis is Mayo Stage IV AL amyloidosis.

42. The method of claim 40 , wherein the antibody is birtamimab.